Assessment of rare bleeding disorders in adolescents with heavy menstrual bleeding.

INTRODUCTION: There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments. Functional assays, particularly for fibrinolytic and rare platelet function defects, are not robust and not readily available. AIM: We aimed to prospectively evaluate the prevalence of genetic defects associated with rare bleeding disorders and describe alterations of coagulation and fibrinolysis in a cohort of adolescents with HMB. METHODS: We performed a prospective observational cohort study of patients with HMB and unexplained bleeding. The study utilized a next generation sequencing panel and investigational global assays of coagulation and fibrinolysis. Additionally, specific functional assays were performed to help characterize novel variants that were identified. RESULTS: In 10 of the 17 patients (∼59%), genetic variants were identified on molecular testing. Thrombin generation by calibrated thromboelastography was not significantly altered in this patient population. The clot formation and lysis assay showed a trend towards increased fibrinolysis with rapid phase of decline in 23% of the patients. Further corresponding functional assays and study population are described. CONCLUSION: Our study describes a unique correlative model in a homogenous cohort of patients with HMB and unexplained bleeding which may inform future diagnostic algorithms, genotype-phenotype correlations as well as aid in specific targeted treatment approaches. Larger future studies may inform risk stratification of patients and improve health related outcomes in patients with HMB.

Factor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment.

ABSTRACT: Factor XI (FXI) deficiency is a rare bleeding disorder that presents complex challenges in patient assessment and bleeding risk management. Despite generally causing mild to moderate bleeding symptoms, clinical manifestations can vary, and bleeding tendency does not always correlate with FXI plasma levels or genotype. Our manuscript delves into the age-related nuances of FXI deficiency across an individual's lifespan. We emphasize issues faced by specific groups, including neonates and females of reproductive age experiencing abnormal uterine bleeding and postpartum hemorrhage. Older patients present unique challenges and concerns related to the management of bleeding as well as thrombotic complications. The current assortment of diagnostic laboratory assays shows limited success in predicting bleeding risk in the perisurgical setting of patients with FXI deficiency. This review explores the intricate interplay between individual bleeding profiles, surgical sites, and FXI activity levels. We also evaluate the accuracy of existing laboratory assays in predicting bleeding and discuss the potential role of investigational global assays in perioperative assessment. Furthermore, we outline our suggested diagnostic approach to refine treatment strategies and decision making. Available treatment options are presented, including antifibrinolytics, replacement products, and recombinant activated FVII. Finally, we discuss promising nonreplacement therapies for the treatment of rare bleeding disorders that can potentially address the challenges faced when managing FXI deficiency-related bleeding complications.

Risk stratified venous thromboembolism prophylaxis in bariatric patients using a Caprini assessment: practice patterns and opportunities for improvement.

BACKGROUND: Venous thromboembolism (VTE) is rare after bariatric surgery but is the most common cause of mortality. The use of VTE risk-stratification tools and compliance with practice guidelines remain unclear. OBJECTIVES: Our objectives were to determine the utilization of risk-stratified VTE prophylaxis and its impact on VTE and bleeding outcomes. SETTING: Academic hospital system. METHODS: Roux-en-Y gastric bypass and sleeve gastrectomy (2016-2021) were identified from our electronic health records. Caprini score and VTE prophylaxis regimen were retrospectively determined. VTE prophylaxis consistent with Caprini guidelines was considered appropriate. Outcomes were compared between VTE prophylaxis cohorts. Variables were compared by Kruskal-Wallis test, Pearson χ2 test, and regression models. A P value of <.05 was considered significant. RESULTS: A total of 1849 bariatric cases were analyzed, including 64% Roux-en-Y gastric bypass and 36% sleeve gastrectomy cases. Of these, 70% and 3.7% received appropriate risk-stratified VTE prophylaxis during hospitalization and at discharge. The mean Caprini score was higher in those without appropriate prophylaxis (8.45 versus 8.04; P = .0004). Inpatient and 30- and 90-day VTE rates were .22%, .47%, and .64%. All discharge VTE events occurred in those not receiving appropriate Caprini risk-stratified VTE prophylaxis. Inpatient and 30- and 90-day bleeding complications were .22%, .23%, and .35%. The likelihood of receiving appropriate prophylaxis varied by hospital site, and receiving appropriate prophylaxis was not associated with increased bleeding risk. CONCLUSION: Caprini guideline-indicated VTE prophylaxis can be safely used in bariatric surgery patients and may reduce preventable VTE complications without increasing bleeding risk.

Low-dose aspirin for prevention of cardiovascular mortality in patients with type 2 diabetes and chronic kidney disease: A real-world nationwide cohort study.

AIMS/INTRODUCTION: Cardiovascular mortality risk is elevated among patients with diabetes and concurrent chronic kidney disease. However, controversy surrounds the use of aspirin for primary prevention within this population. This study aims to assess the effectiveness and safety of low-dose aspirin for primary prevention in patients with diabetes and pre-end-stage renal disease. MATERIALS AND METHODS: This was a retrospective population-based cohort study using the National Health Insurance Research Database in Taiwan. The study included adults with type 2 diabetes who were enrolled in the pre-end-stage renal disease pay-for-performance program and had no atherosclerotic cardiovascular disease. We used propensity score analysis to control baseline characteristics between the two groups. Clinical outcomes including cardiovascular mortality, all-cause mortality, major bleeding, and renal disease progression were compared between patients who first received aspirin and those who did not. RESULTS: Between January 2012 and December 2015, a total of 2,155 low-dose aspirin users and 6,737 nonaspirin users were identified. Following propensity score adjustment, aspirin use exhibited a comparable risk of cardiovascular death compared with nonaspirin users (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.65-1.95; P = 0.681). The risk of all-cause mortality was similar between the two groups (aHR 1.07; 95% CI 0.92-1.24; P = 0.385). Similar risks were observed in terms of major bleeding and renal disease progression. CONCLUSIONS: In patients with diabetes and pre-end-stage renal disease who lacked atherosclerotic cardiovascular disease, low-dose aspirin did not demonstrate a reduction in mortality. These findings do not support the use of aspirin for primary prevention in this high-risk population.

Clinical Assessment of Low Calcium In traUMa (CALCIUM).

Major trauma frequently occurs in the deployed, combat setting and is especially applicable in the recent conflicts with explosives dominating the combat wounded. In future near-peer conflicts, we will likely face even more profound weapons including mortars and artillery. As such, the number of severely wounded will likely increase. Hypocalcemia frequently occurs after blood transfusions, secondary to the preservatives in the blood products; however, recent data suggests major trauma in and of itself is a risk factor for hypocalcemia. Calcium is a major ion involved in heart contractility; thus, hypocalcemia can lead to poor contractility. Smaller studies have linked hypocalcemia to worse outcomes, but it remains unclear what causes hypocalcemia and if intervening could potentially save lives. The objective of this study is to determine the incidence of hypocalcemia on hospital arrival and the association with survival. We are seeking to address the following scientific questions, (1) Is hypocalcemia present following traumatic injury prior to transfusion during resuscitation? (2) Does hypocalcemia influence the amount of blood products transfused? (3) To what extent is hypocalcemia further exacerbated by transfusion? (4) What is the relationship between hypocalcemia following traumatic injury and mortality? We will conduct a multicenter, prospective, observational study. We will gather ionized calcium levels at 0, 3, 6, 12, 18, and 24 hours as part of scheduled calcium measurements. This will ensure we have accurate data to assess the early and late effects of hypocalcemia throughout the course of resuscitation and hemorrhage control. These data will be captured by a trained study team at every site. Our findings will inform clinical practice guidelines and optimize the care delivered in the combat and civilian trauma setting. We are seeking 391 patients with complete data to meet our a priori inclusion criteria. Our study will have major immediate short-term findings including risk prediction modeling to assess who is at risk for hypocalcemia, data assessing interventions associated with the incidence of hypocalcemia, and outcome data including mortality and its link to early hypocalcemia.

Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study.

OBJECTIVE: To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke. STUDY DESIGN AND SETTING: A comparative cohort study in UK general practice data from The Health Improvement Network database. PARTICIPANTS AND INTERVENTIONS: Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint. RESULTS: Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75). CONCLUSIONS: Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.

Cost-effectiveness of Screening for Atrial Fibrillation Using Wearable Devices.

Importance: Undiagnosed atrial fibrillation (AF) is an important cause of stroke. Screening for AF using wrist-worn wearable devices may prevent strokes, but their cost-effectiveness is unknown. Objective: To evaluate the cost-effectiveness of contemporary AF screening strategies, particularly wrist-worn wearable devices. Design Setting and Participants: This economic evaluation used a microsimulation decision-analytic model and was conducted from September 8, 2020, to May 23, 2022, comprising 30 million simulated individuals with an age, sex, and comorbidity profile matching the US population aged 65 years or older. Interventions: Eight AF screening strategies, with 6 using wrist-worn wearable devices (watch or band photoplethysmography, with or without watch or band electrocardiography) and 2 using traditional modalities (ie, pulse palpation and 12-lead electrocardiogram) vs no screening. Main Outcomes and Measures: The primary outcome was the incremental cost-effectiveness ratio, defined as US dollars per quality-adjusted life-year (QALY). Secondary measures included rates of stroke and major bleeding. Results: In the base case analysis of this model, the mean (SD) age was 72.5 (7.5) years, and 50% of the individuals were women. All 6 screening strategies using wrist-worn wearable devices were estimated to be more effective than no screening (range of QALYs gained vs no screening, 226-957 per 100 000 individuals) and were associated with greater relative benefit than screening using traditional modalities (range of QALYs gained vs no screening, -116 to 93 per 100 000 individuals). Compared with no screening, screening using wrist-worn wearable devices was associated with a reduction in stroke incidence by 20 to 23 per 100 000 person-years but an increase in major bleeding by 20 to 44 per 100 000 person-years. The overall preferred strategy was wearable photoplethysmography, followed conditionally by wearable electrocardiography with patch monitor confirmation, which had an incremental cost-effectiveness ratio of $57 894 per QALY, meeting the acceptability threshold of $100 000 per QALY. The cost-effectiveness of screening was consistent across multiple scenarios, including strata of sex, screening at earlier ages (eg, ≥50 years), and with variation in the association of anticoagulation with risk of stroke in the setting of screening-detected AF. Conclusions and Relevance: This economic evaluation of AF screening using a microsimulation decision-analytic model suggests that screening using wearable devices is cost-effective compared with either no screening or AF screening using traditional methods.

Risk of stroke/systemic embolism, major bleeding, and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran, or rivaroxaban compared with warfarin in the United States medicare population: updated analysis.

OBJECTIVE: To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Adults (≥65 years) initiating warfarin or DOACs between 1 January 2013 and 31 December 2014 were selected from the Medicare database and propensity scores matched 1:1 to balance baseline characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major bleeding-related medical costs in each matched cohort. RESULTS: Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38-0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63-0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51-0.63) and dabigatran (HR = 0.80; 95% CI 0.70-0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07-1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs. CONCLUSIONS: This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

The long-term clinical benefits and economic costs associated with increased use of prophylaxis among patients with haemophilia A in China: Population-based predictions from 2018 to 2033.

AIM: To predict the long-term benefits and economic costs of the improvements in haemophilia care in China demonstrated by increasing use of prophylaxis, compared with the current status. METHODS: City-level predictions from 2018 to 2033 were conducted for five representative cities in China. The long-term clinical and economic outcomes in the scenario where haemophilia care has significantly improved and the existing scenario of haemophilia care were calculated and compared. The model input data were obtained from local records, expert interviews, published literature, and other sources. Outcome measures including number of bleeds and joint bleeds, number of target joints, disability rate, direct and indirect costs were calculated at the patient and population levels. RESULTS: The long-term predictions for 2033 demonstrated significantly improved bleed control and joint outcomes due to increased use of prophylaxis. The total number of averted bleed events per patient ranged from 3.9 in Shenyang to 16.1 in Zhengzhou in 2033, and the population-level averted bleed events ranged from 1963 in Xiamen to 14,868 in Zhengzhou. The treatment improvement also leads to significant economic costs driven by increase in clotting factor costs (more than 90%). At the population level, the additional total costs were highest in Zhengzhou (CNY 177.4 million) and lowest in Shenyang (CNY 45.4 million), due to their different population sizes and various existing treatment regimens. The outpatient and hospitalization costs decreased, while the factor costs increased. CONCLUSION: The long-term prophylaxis is associated with avoided bleed events and disabilities. The improved treatment regimens are also associated with a significant economic burden, driven by factor costs.

Use of oral anticoagulants among individuals with cancer and atrial fibrillation in the United States, 2010-2016.

BACKGROUND: Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF). METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016. We used a Cox proportional hazard model and multivariable logistic regression to identify factors associated with anticoagulant use versus no use and direct oral anticoagulants (DOACs) versus warfarin use, respectively. RESULTS: Of 27,702 patients with cancer and NVAF, 4469 (16.1%) used DOACs and 3577 (12.9%) used warfarin. Among 8046 anticoagulant users, DOACs use increased from 21.8% in 2011 to 76.2% in 2016, with a corresponding decline in warfarin use from 78.2% to 23.8%. Nearly 7 out of 10 patients with cancer and NVAF did not initiate anticoagulation in 2016. Anticoagulant use was more likely among those with higher CHA2DS2-VASc scores (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.27-1.90 for score ≥6 vs. 1) or with lower HAS-BLED scores (HR 1.96, 95% CI 1.67-2.30 for score 1 vs. ≥6). Among anticoagulant users, DOAC use was less likely than warfarin in those with higher CHA2DS2-VASc scores (odds ratio [OR] 0.53, 95% CI 0.33-0.84 for score ≥6 vs. 1). CONCLUSIONS: Nearly 7 out of 10 patients with cancer and NVAF did not receive anticoagulation. Use of DOACs increased from 2010 to 2016, with a corresponding decline in warfarin use. DOACs are used less than warfarin among those at higher risk of stroke.

Assessment of global coagulation function under treatment with emicizumab concomitantly with bypassing agents in haemophilia A with inhibitor (UNEBI Study): multicentre open-label non-randomised clinical trial.

INTRODUCTION: Subcutaneous emicizumab prophylaxis substantially reduces bleeding episodes in patients with haemophilia A (PwHA) and factor VIII inhibitor. However, thrombotic events occurred in some PwHA with inhibitor who had received high cumulative doses of activated prothrombin complex concentrates at their breakthrough bleeds, when they were also given prophylactic emicizumab. After that, although the recommended guidance was proposed for bypassing agents (BPAs) therapy under emicizumab prophylaxis for haemostatic management, detailed investigation(s) is(are) required to elucidate the safe and appropriate dose of BPAs to use concomitantly with emicizumab prophylaxis. METHODS AND ANALYSIS: In the UNEBI Study, 60 PwHA with inhibitor will be enrolled for a maximum duration of 3 years, and samples of 20 events following concomitant use of BPAs with emicizumab will be collected. An 'event' is defined as obtaining blood samples before and after administration of BPA when a breakthrough bleed or a surgical procedure occurs. The coagulation potential in the obtained samples will be measured by global coagulation assays. The primary endpoint is the degree of improvement in the maximum coagulation rate by clot waveform analysis (CWA) before and after administration of fixed-dose BPAs. This parameter obtained from CWA, which is triggered with an optimally diluted mixture of prothrombin time/activated partial thromboplastin time-reagents, is reported to be an excellent marker for assessing the degree of improvement in coagulation potential in emicizumab-treated plasma. ETHICS AND DISSEMINATION: The UNEBI Study was approved by the Japan Certified Review Board of Nara Medical University. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: jRCTs051190119.

Cardiac output measurements during high-risk Cesarean section using electrical bioreactance or arterial waveform analysis: assessment of agreement.

OBJECTIVE: Maternal hemodynamics change significantly during Cesarean section complicated by massive hemorrhage or severe hypertensive disease. Cardiac output (CO) monitoring aids early, goal-directed hemodynamic therapy. The aim of this study was to record hemodynamic changes observed during Cesarean section in pregnancies at high risk of hemodynamic instability, using invasive (LiDCOrapid™) and non-invasive (NICOM®) devices, and to assess agreement between the two devices in measuring CO. METHODS: Simultaneous intraoperative hemodynamic measurements were taken using the LiDCOrapid and NICOM devices, following standardized techniques, in women at high risk of hemodynamic instability undergoing Cesarean section. Agreement in CO measurements between the two devices was assessed using Bland-Altman plots and the agreement:tolerability index (ATI). Agreement analyses were performed for repeated measures in subjects, using centiles. RESULTS: From 10 women, 307 paired measurements were analyzed. Mean bias (defined as the mean difference in CO measurements between the LiDCOrapid and NICOM devices) was 3.05 (95% CI, 1.89 to 4.21) L/min. Limits of agreement ranged from -1.58 (95% CI, -4.47 to -0.14) to 7.68 (95% CI, 6.24 to 10.56) L/min. The resulting agreement interval was 9.26 L/min which returned an ATI of 2.3. CONCLUSIONS: There are large mean differences between CO measurements obtained during Cesarean section using the LiDCOrapid and NICOM hemodynamic monitors in pregnant women at high risk of hemodynamic instability, indicating that they should not be considered interchangeable clinically. There is an unacceptably low level of agreement (ATI > 2) in CO measurements between the devices, conferring a high risk of clinical misclassification during massive hemorrhage. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Erythropoietin and blood loss in selected orthopedic procedures]. / Erytropoetyna a utrata krwi w wybranych zabiegach ortopedycznych.

Orthopedic surgical procedures, especially in the lower limbs, are associated with a high risk of massive bleeding and, consequently, the development of anemia and the need for blood transfusions and its preparations. This creates the need to look for effective methods of prevention and treatment of anemia that will be safe for the patient and reduce the cost of treatment. One of the most common methods of limiting the allogenic blood usage in orthopedic procedures is the use of autologus transfusions. In addition to many benefits, they may contribute to the patient's anemia, which is a serious health problem in the post-operative period. Analyzed data from the literature indicate that the use of recombinant human erythropoietin significantly reduces the need for blood transfusion in the perioperative period and may reduce the cost of treatment.

The Assessment of the Risk of Acute Kidney Injury in Patients Undergoing an Urgent Endovascular Treatment Due to Severe Renal Bleeding.

INTRODUCTION: This study was designed to assess the clinical factors associated with the development of acute kidney injury (AKI) in patients undergoing endovascular treatment during the course of severe renal bleeding. METHODS: A retrospective analysis was performed of 36 consecutive patients who were treated endovascularly between January 2006 and December 2016 for anemia caused by iatrogenic (26 pts) or posttraumatic (10 pts) renal bleeding. Typical patient data, baseline, and postprocedural blood parameters were evaluated. As a predictor of AKI occurrence, SCr0 > 1.5 mg/dL, eGFR < 60 ml/min/1.73 m2, and Mehran score were evaluated. RESULTS: Fourteen patients (39%) developed AKI after CM injection. Time of hospitalization (p = 0.02), hypotension (p = 0.005), dialysis (p = 0.05), blood transfusions (p = 0.028), amount of blood received (p = 0.003), red blood units > 3 (RBU) (p = 0.032), and CM > 150 ml (p = 0.014) were related to AKI occurrence. The Mehran score may be used as a predictor of AKI occurrence (p = 0.022). The SCr > 1.5 mg/dL and eGFR < 60 ml/min/1.73 m2 were not statistically significant. Selective renal embolization (mean 34% loss of renal tissue) does not lead to AKI. CONCLUSIONS: Hypotension, anemia requiring blood transfusion, and administration of CM exceeding 150 ml poses higher risk of AKI development, which leads to longer hospital stay and need of dialysis. The Mehran score may be used as predictor of AKI occurrence. Up to one third of the kidney was embolized with no AKI linked to the procedure. The concern of AKI occurrence should not be a cause of delay of endovascular treatment.

The Incidence of Menstrual Regulation Procedures and Abortion in Bangladesh, 2014.

CONTEXT: Menstrual regulation (MR) has been part of the Bangladesh family planning program since 1979. However, clandestine abortion remains a serious health problem in Bangladesh, and anecdotal reports indicate that clandestine use of misoprostol has increased since the most recent estimates (for 2010). Because of this, it is important to assess changes in the use of MR services and the incidence of clandestine abortion since 2010. METHODS: A survey of a nationally representative sample of 829 health facilities that provide MR or postabortion care services and a survey of 322 professionals knowledgeable about these services were conducted in 2014. Direct and indirect methods were applied to calculate the incidence of MR and induced abortion. RESULTS: In 2014, an estimated 1,194,000 induced abortions were performed in Bangladesh (29 per 1,000 women aged 15-49), and 257,000 women were treated for complications of such abortions (a rate of 6 per 1,000 women aged 15-49). Among women with complications, the proportion presenting with hemorrhage increased significantly, from 27% to 48%. An estimated 430,000 MR procedures (using MVA or medication) were performed in health facilities nationwide, a decline of about 40% in the MR rate-from 17 to 10 per 1,000 women aged 15-49-from 2010 to 2014. CONCLUSIONS: Given declines in MR provision, more attention needs to be paid to building capacity, including hiring and training more providers of MR. Harm-reduction approaches should be pursued to increase the safety of clandestine use of misoprostol in Bangladesh.

Ethnic differences in maternal near miss.

PURPOSE: To evaluate the association between ethnic differences and the occurrence of maternal near miss (MNM) in the Amazon and Northeast regions of Brazil. METHODS: This is a secondary analysis of a national cross-sectional study focused on the assessment of care to pregnancy, childbirth, and infants under 1 year of age. Ethnicity was classified as white, black or indigenous. Ethnic distribution by state and region, the proportion of severe maternal complications and related procedures, and the prevalence of MNM and its criteria were calculated for the ethnic groups. Risks for MNM were estimated per sociodemographic characteristics and healthcare received by ethnic group, using prevalence ratios adjusted by all predictors and by the sampling method. RESULTS: 76% of the 16.783 women were black, 20% white and 3.5% indigenous. Around 36% reported any complication related to pregnancy and the most frequent were hemorrhage (27-31%), and infection (7.1-9.0%). The MNM ratio was higher among indigenous (53.1) and black (28.4) than in white women (25.7). For black women, the risks of MNM were lower for private prenatal care and hospital admission for conditions other than hypertension, while higher for cesarean section and peregrination. For indigenous, the risks of MNM were lower for private prenatal care, and higher for a longer time to reach the hospital. For white women, only the low number of prenatal visits increased the risk of MNM. CONCLUSIONS: The occurrence of MNM was higher for indigenous and black than for white women.

Real-world resource use and costs of haemophilia A-related bleeding.

INTRODUCTION: Prophylaxis treatment is recommended for haemophilia patients, but associated real-world economic costs and potential cost-savings associated with improved disease management are not fully known. This study aimed to assess haemophilia A-related resource use and cost by treatment type (prophylaxis versus non-prophylaxis) and any associated cost-savings. METHODS: Truven MarketScan Commercial claims data (2004-2012) were used to identify haemophilia A-related healthcare utilization, healthcare costs and patterns of prophylaxis and non-prophylaxis treatment among 6- to 64-year-old males. We estimated bleeding-related resource utilization and costs in three age groups (6-18, 19-44, 45-64) by treatment types and assessed the extent to which early initiation of prophylactic treatment can mitigate them. T-tests and ordinary least squares regressions were used to compare unadjusted and demographics-adjusted cost estimates. RESULTS: Among children, overall haemophilia- and bleeding-related non-pharmacy costs were substantially lower for patients receiving prophylaxis (haemophilia-related: $15,864 vs. $53,408; P < 0.001; bleeding-related: $696 vs. $2013, respectively; P = 0.04). Among younger adults (19-44), haemophilia-related non-pharmacy costs were lower for patients receiving prophylaxis ($22,028 vs. $56,311, respectively; P = 0.001). Among children, these savings fully offset the incremental pharmacy cost due to prophylaxis. Among younger adults, the savings offset approximately 34% of the incremental pharmacy cost. No differences were found for older adults (45-64). CONCLUSION: These results suggest that initiating prophylaxis earlier in life may reduce the healthcare costs of bleeding events and their long-term complications. Future studies should strive to collect more detailed information on disease severity and treatment protocols to improve estimates of disease burden.

1: 1 Transfusion strategies are right for the wrong reasons.

BACKGROUND: Early assessment of clot function identifies coagulopathies after injury. Abnormalities include a hypercoagulable state from excess thrombin generation, as well as an acquired coagulopathy. Efforts to address coagulopathy have resulted in earlier, aggressive use of plasma emphasizing 1:1 resuscitation. The purpose of this study was to describe coagulopathies in varying hemorrhagic profiles from a cohort of injured patients. METHODS: All injured patients who received at least one unit of packed red blood cells (PRBC) in the first 24 hours of admission from September 2013 to May 2015 were eligible for inclusion. Group-Based Trajectory Modeling, using volume of transfusion over time, was used to identify specific hemorrhagic phenotypes. The thromboelastography profile of each subgroup was characterized and group features were compared. RESULTS: Four hemorrhagic profiles were identified among 330 patients-minimal (MIN, group 1); patients with large PRBC requirements later in the hospital course (LH, group 2); massive PRBC usage (MH, group 3), and PRBC transfusion limited to shortly after injury (EH, group 4). All groups had an R-time shorter than the normal range (3.2-3.5, p = NS). Patients in group 3 had longer K-times (1.8 vs. 1.2-1.3, p < 0.05), significantly flatter α-angles (66.7 vs. 70.4-72.8, p < 0.05), and significantly weaker clot strength (MA 54.6 vs. 62.3-63.6, p < 0.05). Group 3 had greater physiologic derangements at admission and worse overall outcomes. CONCLUSION: Hemorrhagic profiles suggest a rapid onset of clot formation in all subgroups but significantly suppressed thrombin burst and diminished clot strength in the most injured. Patients are both hypercoagulable, with early and precipitous clot formation, and also have a demonstrable hypocoagulability. The exact cause of traumatic hypocoagulability is likely multifactorial. Goal-directed resuscitation, as early as institution of the massive transfusion protocol, may be more effective in resuscitating the most coagulopathic patients. LEVEL OF EVIDENCE: Prognostic study, level III.

A prospective study of health-related quality of life of boys with severe haemophilia A in China: comparing on-demand to prophylaxis treatment.

INTRODUCTION: Treatment for boys with haemophilia in China is rapidly improving; however, comprehensive outcomes have not been examined prospectively. AIM: The aim of this study was to evaluate the effect of short-term full-dose prophylaxis compared to on-demand treatment, on the Health-Related Quality of Life (HR-QoL) of boys with severe haemophilia A (HA) in China. METHODS: Boys with severe HA (FVIII<1%) completed 3 months of on-demand treatment and 3 months of full-dose prophylaxis (25 FVIII IU per kg 3x per week). The primary outcomes were child- and parent-reported Canadian Hemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) scores. The number and type of bleeds and Activities Scale for Kids (ASK) scores were also recorded. RESULTS: Analyses included 23 boys between 4 and 15.9 years of age. The number of bleeds decreased by 94% on prophylaxis (P < 0.0001, Wilcoxon Signed-Rank test). The mean child-reported CHO-KLAT scores for boys ≥7 years (n = 20) was 61.4 (±10.9) during on-demand treatment and 61.9 (±11.4) following short-term prophylaxis (P = 0.72, paired t-test). The mean parent-reported CHO-KLAT score during the on-demand phase was 54.4 (±10.5) with an increase of 3.8 points (±8.1; P = 0.04, paired t-test) following prophylaxis. CONCLUSIONS: Child-reported CHO-KLAT scores were lower in boys with severe HA in China than reported in countries with access to full-dose prophylaxis. Boys reported higher HR-QoL scores than their parents. Small improvements in ASK scores were noted following the prophylaxis phase. These changes were only significant in the parent-reported CHO-KLAT scores. Longer term prospective clinical trials are needed in China to determine the impact of prophylaxis on HR-QoL in boys with severe HA.