The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework.
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ABSTRACT:
SUBMITTER: Lin Y
PROVIDER: S-EPMC3546370 | biostudies-other | 2012 Dec
REPOSITORIES: biostudies-other
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The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework.
Lin Y Y Moltzan C J CJ Anderson D R DR
Transfusion medicine (Oxford, England) 20120527 6
In 2006, the Canadian National Advisory Committee on Blood and Blood Products (NAC) developed a transfusion policy framework for the use of off-label recombinant factor VIIa (rFVIIa) in massive bleeding. Because the number of randomised controlled trials has doubled, the NAC undertook a review of the policy framework in 2011. On the basis of the review of 29 randomised controlled trials, there remains little evidence to support the routine use of rFVIIa in massive bleeding. Mortality benefits ha ...[more]
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Project description:Background: Massive transfusion in patients with upper gastrointestinal bleeding (UGIB) was not investigated. We developed a new scoring system to predict massive transfusion and to enhance care and early resource mobilization. Methods: Massive transfusion was defined as transfusion with ≥10 units of red blood cells within the first 24 h. Data were extracted from a 10-year, six-hospital database. Logistic regression was applied to derive a risk score for massive transfusion using data from 2006 to 2010, in 24,736 patients (developmental cohort). The score was then validated using data from 2011 to 2015 in 27,449 patients (validation cohort). Area under the receiver operating characteristic (AUROC) curve was performed to assess prediction accuracy. Results: Five characteristics were independently associated (p < .001) with massive transfusion: presence of band-form cells among white blood cells (band form >0), international normalized ratio (INR) >1.5, pulse >100 beats per minute or systolic blood pressure <100 mmHg (shock), haemoglobin <8.0 g/dL and endoscopic therapy. The new scoring system successfully discriminated well between UGIB patients requiring massive transfusion and those who did not in both cohorts (AUROC: 0.831, 95%CI: 0.827-0.836; AUROC: 0.822, 95% CI: 0.817-0.826, respectively). Conclusions: The new scoring system predicts massive transfusion requirement in patients with UGIB well. Key messages Massive transfusion is a life-saving management in massive upper gastrointestinal bleeding. How to identify patients requiring massive transfusion in upper gastrointestinal bleeding is poorly documented. Approximately 3.9% of upper gastrointestinal bleeding patients require massive transfusion. A new scoring system is developed to identify patients requiring massive transfusion with high accuracy.
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Project description:BackgroundDefinitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.MethodsWe systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.ResultsOf the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).ConclusionsTransfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
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Project description:BackgroundThe benefits and risks of off-label use of recombinant factor VIIa in patients without hemophilia are contested. We performed a systematic review to assess the effectiveness and safety of such use.MethodsWe searched electronic databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing recombinant factor VIIa with placebo in any patient population except those with hemophilia up to January 2010. Eligible articles were assessed for inclusion, data were extracted, and study quality was evaluated. Outcomes included mortality, blood loss, requirements for red blood cell transfusion, number of patients transfused and thromboembolic events.ResultsWe identified 26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137) and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic use, we found no significant difference in mortality or thromboembolic events between the treatment and placebo groups. We found modest benefits favouring recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95% confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials, we found a nonsignificant decrease in mortality and a nonsignificant increase in thromboembolic events but no difference in control of bleeding or red blood cell transfusion.InterpretationClinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven. Given its potential risks, such use cannot be recommended, and in most cases, it should be restricted to clinical trials.
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Project description:IntroductionOur aim was to develop consensus guidelines for use of recombinant activated factor VII (rFVIIa) in massive hemorrhage.MethodsA guidelines committee derived the recommendations using clinical trial and case series data identified through searches of available databases. Guidelines were graded on a scale of A-E according to the strength of evidence available. Consensus was sought among the committee for each recommendation.ResultsA recommendation for use of rFVIIa in blunt trauma was made (grade B). rFVIIa might also be beneficial in post-partum hemorrhage (grade E), uncontrolled bleeding in surgical patients (grade E) and bleeding following cardiac surgery (grade D). rFVIIa could not be recommended for use: in penetrating trauma (grade B); prophylactically in elective surgery (grade A) or liver surgery (grade B); or in bleeding episodes in patients with Child-Pugh A cirrhosis (grade B). Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child-Pugh B and C cirrhosis (grade C). Monitoring of rFVIIa efficacy should be performed visually and by assessment of transfusion requirements (grade E), while thromboembolic adverse events are a cause for concern. rFVIIa should not be administered to patients considered unsalvageable by the treating medical team.ConclusionsThere is a rationale for using rFVIIa to treat massive bleeding in certain indications; however, only adjunctively to the surgical control of bleeding once conventional therapies have failed. Lack of data from randomized, controlled clinical trials, and possible publication bias of the case series data, limits the strength of the recommendations that can be made.
| S-EPMC1750973 | biostudies-literature
Project description:BackgroundIn people with haemophilia, therapeutic clotting agents might be recognised as a foreign protein and induce anti-factor VIII antibodies, known as 'inhibitors'. Drugs insensitive to such antibodies, either recombinant or plasma-derived, are called factor VIII 'by-passing' agents and used for treatment of bleeding in people with inhibitors.ObjectivesTo determine the clinical effectiveness of recombinant factor VIIa concentrate compared to plasma-derived concentrates for treating acute bleeding episodes in people with haemophilia and inhibitors.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Coagulopathies Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Coagulopathies Trials Register: 23 September 2015.Selection criteriaRandomised and quasi-randomised controlled clinical trials comparing recombinant factor VIIa concentrate to human plasma-derived concentrates (high-dose human or recombinant factor VIII or factor IX concentrate; non-activated prothrombin complex concentrates; activated prothrombin complex concentrates) in people with haemophilia. Comparisons with animal-derived products were excluded.Data collection and analysisTwo authors independently assessed the trials (eligibility and risk of bias) and extracted data. No combined meta-analyses were performed due to the unavailability of outcomes and comparisons common to the included trials.Main resultsA total of 15 trials were identified, two of which (with data for a total of 69 participants) were eligible for analysis. Both trials showed methodological flaws and did not show superiority of one treatment over the other. Both the treatments showed that recombinant factor VIIa and activated prothrombin complex concentrate appeared to have a similar haemostatic effect in both trials, without increasing thromboembolic risk.Authors' conclusionsBased on the separate analysis of the two available randomised trials, recombinant factor VIIa and activated prothrombin complex concentrate were found to be similar in efficacy and safety. However, there is a need for further, well-designed, adequately-powered, randomised controlled trials to assess the relative benefits and risks of using recombinant factor VIIa compared to human plasma-derived concentrates in people with haemophilia with inhibitors. It is advisable that researchers in the field define commonly agreed objective outcome measures in order to enable the pooling of their results, thus increasing the power of comparisons. To date, data could not be combined in a formal meta-analysis. For the same reason reporting concordant and discordant pairs in cross-over trials is recommended.
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Project description:BackgroundCalls have been made for greater application of the decision sciences to investigate and improve use of research evidence in mental health policy and practice. This article proposes a novel method, "decision sampling," to improve the study of decision-making and research evidence use in policy and programmatic innovation. An illustrative case study applies the decision sampling framework to investigate the decisions made by mid-level administrators when developing system-wide interventions to identify and treat the trauma of children entering foster care.MethodsDecision sampling grounds qualitative inquiry in decision analysis to elicit information about the decision-making process. Our case study engaged mid-level managers in public sector agencies (n = 32) from 12 states, anchoring responses on a recent index decision regarding universal trauma screening for children entering foster care. Qualitative semi-structured interviews inquired on questions aligned with key components of decision analysis, systematically collecting information on the index decisions, choices considered, information synthesized, expertise accessed, and ultimately the values expressed when selecting among available alternatives.ResultsFindings resulted in identification of a case-specific decision set, gaps in available evidence across the decision set, and an understanding of the values that guided decision-making. Specifically, respondents described 14 inter-related decision points summarized in five domains for adoption of universal trauma screening protocols, including (1) reach of the screening protocol, (2) content of the screening tool, (3) threshold for referral, (4) resources for screening startup and sustainment, and (5) system capacity to respond to identified needs. Respondents engaged a continuum of information that ranged from anecdote to research evidence, synthesizing multiple types of knowledge with their expertise. Policy, clinical, and delivery system experts were consulted to help address gaps in available information, prioritize specific information, and assess "fit to context." The role of values was revealed as participants evaluated potential trade-offs and selected among policy alternatives.ConclusionsThe decision sampling framework is a novel methodological approach to investigate the decision-making process and ultimately aims to inform the development of future dissemination and implementation strategies by identifying the evidence gaps and values expressed by the decision-makers, themselves.
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Project description:BackgroundAppropriate blood component transfusion might differ between intraoperative massive bleeding and traumatic massive bleeding in the emergency department because trauma patients initially bleed undiluted blood and replacement typically lags behind blood loss. We compared these two blood loss scenarios, intraoperative and traumatic, using a computer simulation.MethodsWe modified the multi-compartment dynamic model developed by Hirshberg and implemented it using STELLA 9.0. In this model, blood pressure changes as blood volume fluctuates as bleeding rate and transcapillary refill rate are controlled by blood pressure. Using this simulation, we compared the intraoperative bleeding scenario with the traumatic bleeding scenario. In both scenarios, patients started to bleed at a rate of 50 ml/min. In the intraoperative bleeding scenario, fluid was administered to maintain isovolemic status; however, in the traumatic bleeding scenario, no fluid was supplied for up to 30 min and no blood was supplied for up to 50 min. Each unit of packed red blood cells (PRBC) was given when the hematocrit decreased to 27%, fresh frozen plasma (FFP) was transfused when plasma was diluted to 30%, and platelet concentrate (PC) was transfused when platelet count became 50,000/ml.ResultsIn both scenarios, the appropriate ratio of PRBC:FFP was 1:0.47 before PC transfusion, and the ratio of PRBC:FFP:platelets was 1:0.35:0.39 after initiation of PC transfusion.ConclusionThe ratio of transfused blood component did not differ between the intraoperative bleeding and traumatic bleeding scenarios.
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Project description:Our aim was to study the impact of bleeding and red blood cell (RBC) resuscitation on liver regeneration. We assessed the impact of RBC storage time on liver regeneration following 50% partial hepatectomy (PHx) in rats, and explored possible contributing molecular mechanisms using immunohistochemistry, RNA-Seq, and macrophage depletion.
2022-11-14 | GSE216924 | GEO
Project description:ObjectiveTo describe the development of a framework for monitoring and evaluating knowledge translation (KT) networks.MethodThe framework was developed using mixed methods over four phases, including i) a targeted literature review of KT networks, activities and indicators, ii) two scoping reviews to further enhance the set of indicators, iii) peer-reviews by international KT experts and an online expert consultation, and iv) piloting.ResultsA comprehensive theory of change (ToC) and indicators, both for the Network Secretariat and its participating member countries, were identified to develop the monitoring and evaluation framework. The framework includes (i) a ToC, including three key indicator domains across the results chain (outputs, short term outcomes, intermediate outcomes), and (ii) indicators for the three key domains, that can be selected depending on the stage of network maturity, along with suggested data collection methods. The three key indicator domains are 1) KT capacity and skill building; 2) network (structure, governance and leadership); and 3) KT/evidence-informed policy value and culture.ConclusionThe monitoring and evaluation framework that links KT activities with policy and health outcomes fills an important gap in optimizing KT procedures, generating lessons learned and increasing accountability of major multipartner KT networks.
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Project description:Recent clinical studies suggest that the prophylactic use of recombinant factor VIIa (rFVIIa) markedly reduces the number of bleeding episodes in hemophilic patients with inhibitors. Given the short biological half-life of rFVIIa, it is unclear how rFVIIa could be effective in prophylactic treatment.To examine the extravascular distribution of pharmacologically administered rFVIIa to obtain clues on how rFVIIa could work in prophylaxis.Recombinant mouse FVIIa tagged with AF488 fluorophore (AF488-FVIIa) was administered into mice via the tail vein. At different time intervals following the administration, mice were exsanguinated and various tissues were collected. The tissue sections were processed for immunohistochemistry to evaluate distribution of rFVIIa.rFVIIa, immediately following the administration, associated with the endothelium lining of large blood vessels. Within 1 h, rFVIIa bound to endothelial cells was transferred to the perivascular tissue surrounding the blood vessels and thereafter diffused throughout the tissue. In the liver, rFVIIa was localized to sinusoidal capillaries and accumulated in hepatocytes. In bone, rFVIIa was accumulated in the zone of calcified cartilage and some of it was retained there for a week. The common finding of the present study is that rFVIIa in extravascular spaces was mostly localized to regions that contain TF expressing cells.The present study demonstrates that pharmacologically administered rFVIIa readily associates with the vascular endothelium and subsequently enters into extravascular spaces where it is likely to bind to TF and is retained for extended time periods. This may explain the prolonged pharmacological effect of rFVIIa.
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