Identifying existing Choosing Wisely recommendations of high relevance and importance to hematology

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE TM relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787–792, 2016. © 2016 Wiley Periodicals, Inc

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Retrospective analysis of bleeding events after central venous catheter placement in thrombotic thrombocytopenic purpura

Background Thrombotic thrombocytopenic purpura (TTP) is a thrombotic disorder caused by severe deficiency of ADAMTS13. Platelets are transfused prophylactically in non-TTP patients for central venous catheter (CVC) with a count \u3c20 × 109/L to prevent bleeding. However, transfusing platelets in TTP prior to CVC placement remains controversial due to concern for arterial thrombosis and mortality. At our center, platelet transfusion is contraindicated in TTP, therefore, we analyzed data for bleeding complications following CVC placement. Study Design and Methods 95 acute episodes of TTP were identified. Twenty-six episodes were excluded for insufficient documentation or no CVC placement. The charts of 69 remaining episodes were reviewed. Results Of 69 TTP episodes, nine (13 %) had bleeding after a CVC placement. Of these, seven bleeds were minor, and the two were major related to the technical issues during femoral venous access causing arterial bleeds. Median platelet count before the CVC placement among those experiencing bleeding complications was 12 × 109/L (range 3–44) as compared to median count of 15 × 109/L (range 4–257) in those who did not bleed (p = 0.258). Among 44 episodes with a platelet count \u3c20 × 109/L, seven (16 %) had bleeds. Conclusion Major bleeding complications following CVC placement in TTP is uncommon and most likely related to technical challenges. Median platelet count was similar in patients who bled versus those who did not, suggesting that platelet transfusion is unnecessary to correct platelet count prior to a CVC placement in TTP

Can an anti-Xa assay for low-molecular-weight heparin be used to assess the presence of rivaroxaban?

BACKGROUND: Due to the convenience afforded by the lack of required laboratory monitoring, direct oral anticoagulants (DOACs) are increasingly used as alternatives to Vitamin-K antagonists for certain medical conditions. However, there are circumstances in which assessment of DOAC plasma concentrations may be helpful in guiding clinical decisions, including patients presenting with either bleeding or thrombosis, or patients requiring urgent invasive procedures. Evaluating the anticoagulant effects of DOACs is often difficult because of the limited availability of DOAC-specific assays in most laboratories. OBJECTIVE: To evaluate the correlation between ex vivo plasma concentrations of rivaroxaban and a chromogenic anti-Xa assay for low-molecular-weight heparin (LMWH) routinely used in our coagulation laboratory. MATERIALS AND METHODS: Twenty-nine blood samples from 20 patients anticoagulated with rivaroxaban (dose; 10-20 mg/day) were evaluated using an anti-Xa assay for LMWH and results were correlated with rivaroxaban plasma concentrations using a rivaroxaban specific assay. RESULTS: A linear dose-dependent relationship was demonstrated between plasma concentrations of rivaroxaban and the chromogenic anti-Xa assay for LMWH (R2 = 0.92). PT and PTT demonstrated poor correlations (R2 = 0.03; and R2 = 0.01, respectively) with rivaroxaban plasma concentrations. CONCLUSION: Findings from this study suggest that if specific assays for rivaroxaban are unavailable, then the chromogenic anti-Xa assay for LMWH may be useful for assessing the anticoagulant effects of rivaroxaban

A Massive Transfusion Protocol to Decrease Blood Component Use and Costs

Hypothesis A massive transfusion protocol (MTP) decreases the use of blood components, as well as turnaround times, costs, and mortality. Design Retrospective before-and-after cohort study. Setting Academic level I urban trauma center. Patients and Methods Blood component use was compared in 132 patients during a 2-year period following the implementation of an MTP; 46 patients who were treated the previous year served as historical control subjects. Intervention Introduction of an MTP that included recombinant factor VIIa for patients with exsanguinating hemorrhage. Main Outcome Measures The amount of each blood component transfused, turnaround times, blood bank and hospital charges, and mortality rates. Results After introduction of the MTP, there was a significant decrease in packed red blood cells, plasma, and platelet use. The turnaround time for the first shipment was less than 10 minutes, and the time between the first and second shipments was reduced from 42 to 18 minutes, compared with historical controls. The decreased use of blood products represented a savings of $2270 per patient or an annual savings of$200 000, despite increased costs for recombinant factor VIIa. There was no difference in mortality in either group; it remained around 50%. Thromboembolic complications did not increase, despite a significant increase in the use of recombinant factor VIIa. Conclusions The MTP resulted in a reduction in the use of blood components with improved turnaround times and significant savings. Mortality was unaffected. The use of recombinant factor VIIa did not increase thromboembolic complications in these patients. Massive transfusion is loosely defined as the transfusion of more than 10 units of packed red blood cells (PRBCs) in a 24-hour period.1,2 Although there have been reports of improved survival after massive transfusion during the last decade, it is unclear what factors are responsible.3 There is increasing evidence that the early coagulopathy seen in trauma patients should be treated aggressively during the initial resuscitation, particularly in those patients requiring massive transfusion.4,5 It has been suggested that a protocol designed to give red blood cells and coagulation factors (ie, plasma and platelets) in prespecified ratios can improve outcomes.6,7 Both military and civilian data suggest that a ratio of 1:1 to 1:2 of fresh frozen plasma to PRBCs is needed to adequately treat coagulopathy in patients undergoing massive transfusions.6,8,9 We developed and instituted a massive transfusion protocol (MTP) at Parkland Health and Hospital System, Dallas, Texas, which was mainly designed for trauma patients with severe, active hemorrhage. The protocol includes giving prespecified amounts of PRBCs, thawed plasma (defined in the “Methods” section), cryoprecipitate, and platelets, as well as the recombinant factor VIIa (rFVIIa). The rationale of this protocol was to improve turnaround time, ie, the time between when the order for the products was received in the blood bank and when the products left the blood bank, as well as to provide component therapy in a more clearly defined proportion to prevent and treat coagulopathy and to reduce the waste that occurred with random product ordering. We sought to examine our experience and outcomes among patients treated using this protocol. We hypothesized that an MTP would improve turnaround times, reduce the use of blood products and associated charges, and possibly decrease mortality

A Massive Transfusion Protocol to Decrease Blood Component Use and Costs

Hypothesis A massive transfusion protocol (MTP) decreases the use of blood components, as well as turnaround times, costs, and mortality. Design Retrospective before-and-after cohort study. Setting Academic level I urban trauma center. Patients and Methods Blood component use was compared in 132 patients during a 2-year period following the implementation of an MTP; 46 patients who were treated the previous year served as historical control subjects. Intervention Introduction of an MTP that included recombinant factor VIIa for patients with exsanguinating hemorrhage. Main Outcome Measures The amount of each blood component transfused, turnaround times, blood bank and hospital charges, and mortality rates. Results After introduction of the MTP, there was a significant decrease in packed red blood cells, plasma, and platelet use. The turnaround time for the first shipment was less than 10 minutes, and the time between the first and second shipments was reduced from 42 to 18 minutes, compared with historical controls. The decreased use of blood products represented a savings of $2270 per patient or an annual savings of$200 000, despite increased costs for recombinant factor VIIa. There was no difference in mortality in either group; it remained around 50%. Thromboembolic complications did not increase, despite a significant increase in the use of recombinant factor VIIa. Conclusions The MTP resulted in a reduction in the use of blood components with improved turnaround times and significant savings. Mortality was unaffected. The use of recombinant factor VIIa did not increase thromboembolic complications in these patients. Massive transfusion is loosely defined as the transfusion of more than 10 units of packed red blood cells (PRBCs) in a 24-hour period.1,2 Although there have been reports of improved survival after massive transfusion during the last decade, it is unclear what factors are responsible.3 There is increasing evidence that the early coagulopathy seen in trauma patients should be treated aggressively during the initial resuscitation, particularly in those patients requiring massive transfusion.4,5 It has been suggested that a protocol designed to give red blood cells and coagulation factors (ie, plasma and platelets) in prespecified ratios can improve outcomes.6,7 Both military and civilian data suggest that a ratio of 1:1 to 1:2 of fresh frozen plasma to PRBCs is needed to adequately treat coagulopathy in patients undergoing massive transfusions.6,8,9 We developed and instituted a massive transfusion protocol (MTP) at Parkland Health and Hospital System, Dallas, Texas, which was mainly designed for trauma patients with severe, active hemorrhage. The protocol includes giving prespecified amounts of PRBCs, thawed plasma (defined in the “Methods” section), cryoprecipitate, and platelets, as well as the recombinant factor VIIa (rFVIIa). The rationale of this protocol was to improve turnaround time, ie, the time between when the order for the products was received in the blood bank and when the products left the blood bank, as well as to provide component therapy in a more clearly defined proportion to prevent and treat coagulopathy and to reduce the waste that occurred with random product ordering. We sought to examine our experience and outcomes among patients treated using this protocol. We hypothesized that an MTP would improve turnaround times, reduce the use of blood products and associated charges, and possibly decrease mortality

Method agreement analysis and interobserver reliability of the ISTH proposed definitions for effective hemostasis in management of major bleeding

Introduction In 2016 the Scientific and Standardization Subcommittee (SSC) on Control of Anticoagulation of the International Society on Thrombosis and Haemostasis (ISTH) proposed criteria to evaluate the effectiveness of anticoagulant reversal in major bleeding management. Testing and validation of these criteria are required. Objective To investigate the method agreement, interobserver reliability and applicability of the ISTH proposed definitions for hemostatic effectiveness. Methods Patient data from three anticoagulant-antidote studies were used for hemostatic effectiveness assessment using the ISTH-proposed definitions and clinical opinion. For every patient a case document was produced. For each cohort, four adjudicators were asked to assess the hemostatic effectiveness independently on a case-by-case basis. Agreement between the two methods of hemostatic effectiveness assessment was calculated using Cohen's kappa (), with a calculated sample size of at least 73 cases. Results The full dataset consisted of 116 cases, resulting in 464 assessments. Method agreement in outcome was observed in 364 of 464 assessments (78.5%), resulting in of 0.634 (95% CI: 0.575-0.694), or substantial agreement. Interobserver reliability analysis of the proposed definitions computed an overall agreement of 54.2% with of 0.312 (fair agreement). Discussion Method agreement analysis shows that the conclusions drawn using the ISTH definitions have substantial agreement with clinical opinion. Interobserver reliability analysis demonstrated acceptable agreement. In-depth analysis provided minor opportunities for further improvement and correct application of the definition. The definition is recommended to be used in all future studies evaluating hemostatic effectiveness, taking the suggested recommendations into account