Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy

Balvers, Kirsten; Dieren, Susan van; Baksaas-Aasen, Kjersti; Gaarder, Christine; Brohi, Karim; Eaglestone, Simon; Stanworth, Simon; Johansson, Pär I.; Ostrowski, Sisse Rye; Stensballe, Jakob; Maegele, Marc; Goslings, J. Carel; Juffermans, Nicole P.

doi:10.1002/bjs.10330

Cited by 45 publications

(45 citation statements)

References 32 publications

(29 reference statements)

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“…In 2013, Holcomb et al 20 published findings of the PROMMTT (Prospective, Observational, Multicenter, Major Trauma Transfusion) study showing that although only 72% of patients received platelets within 3 hours, the early delivery of higher platelet and plasma ratios was associated with decreased 24-hour mortality. Similar conclusions were drawn from the ACIT (Activation of Coagulation and Inflammation in Trauma) study, where Balvers et al 21 reported higher ratios of platelets or plasma/RBCs, in combination with tranexamic acid, reduced both the rate of massive transfusion and the incidence of mortality in a comparable patient population. Furthermore, in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial, a significant increase in the incidence of hemostasis and a reduction in exsanguinating deaths were found in patients receiving a higher ratio of platelets and plasma/RBCs.…”

Section: Introductionsupporting

confidence: 70%

Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial

Xu²,

et al. 2018

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Key Points• Early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding trauma patients.Transfusing platelets during massive hemorrhage is debated because of a lack of high-quality evidence concerning outcomes in trauma patients. The objective of this study was to examine the effect of platelet transfusions on mortality in severely injured trauma patients. This work analyzed PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial patients who received only the first cooler of blood products, which either did or did not contain platelets. Primary outcomes were all-cause mortality at 24 hours and 30 days and hemostasis.Secondary outcomes included cause of death, complications, and hospital-, intensive care unit (ICU)-, and ventilator-free days. Continuous variables were compared using Wilcoxon rank sum tests. Categorical variables were compared using Fisher's exact tests. There were 261 PROPPR patients who achieved hemostasis or died before receiving a second cooler of blood products (137 received platelets and 124 did not). Patients who received platelets also received more total plasma (median, 3 vs 2 U; P , .05) by PROPPR intervention design.There were no differences in total red blood cell transfusions between groups. After controlling for plasma volume, patients who received platelets had significantly decreased 24-hour (5.8% vs 16.9%; P , .05) and 30-day mortality (9.5% vs 20.2%; P , .05). More patients in the platelet group achieved hemostasis (94.9% vs 73.4%; P , .01), and fewer died as a result of exsanguination (1.5% vs 12.9%; P , .01). Patients who received platelets had a shorter time on mechanical ventilation (P , .05); however, no differences in hospital-or ICU-free days were observed. In conclusion, early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding patients. This trial was registered at www.clinicaltrials.gov as # NCT01545232.

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Section: Introductionsupporting

confidence: 70%

Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial

Xu²,

et al. 2018

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“…This is also in line with the iTACTIC protocol [167]. In severe traumatic hemorrhage, fixed-ratio RBC and plasma transfusion is not effective to treat ATC and to reduce mortality [12][13][14][15][16][17]171]. Innerhofer et al compared in their RCT the efficacy of ROTEM-guided administration of coagulation factor concentrates (fibrinogen, factor XIII, and four-factor PCC) versus plasma transfusion to treat ACT and to stop bleeding [172,173].…”

Section: In Trauma and Orthopedic Surgerymentioning

confidence: 79%

“…Ratio-based transfusion concepts do not correct coagulopathy and do not reduce mortality in patients with severe hemorrhage [13][14][15][16][17]. Ratio-based concepts do not stop bleeding.…”

Section: Introductionmentioning

confidence: 99%

The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

Görlinger

Pérez-Ferrer

Dirkmann

et al. 2019

Korean J Anesthesiol

163

138

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Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic method and enables to assess viscoelastic profiles of whole blood in various clinical settings. ROTEM-guided bleeding management has become an essential part of patient blood management (PBM) which is an important concept in improving patient safety. Here, ROTEM testing and hemostatic interventions should be linked by evidence-based, setting-specific algorithms adapted to the specific patient population of the hospitals and the local availability of hemostatic interventions. Accordingly, ROTEM-guided algorithms implement the concept of personalized or precision medicine in perioperative bleeding management ('theranostic' approach). ROTEM-guided PBM has been shown to be effective in reducing bleeding, transfusion requirements, complication rates, and health care costs. Accordingly, several randomized-controlled trials, meta-analyses, and health technology assessments provided evidence that using ROTEM-guided algorithms in bleeding patients resulted in improved patient's safety and outcomes including perioperative morbidity and mortality. However, the implementation of ROTEM in the PBM concept requires adequate technical and interpretation training, education and logistics, as well as interdisciplinary communication and collaboration. Fig. 1. ROTEM trace ('temogram') displaying the clinically most important parameters and their informative value. FDPs: fibrin (ogen) split products. Courtesy of Klaus Görlinger, Germany.

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“…Different definitions of hyperfibrinolysis as detected by VMs used in various studies have been reviewed and summarized elsewhere , and efforts are underway to standardize how diagnosis is performed, and to identify the best parameters to guide therapeutic interventions. For example, research is being carried out by the European TACTIC consortium to develop data‐driven algorithms for the management of hemorrhage .…”

Section: Viscoelastic Methodsmentioning

confidence: 99%

Measuring fibrinolysis: from research to routine diagnostic assays

Longstaff

2018

Journal of Thrombosis and Haemostasis

134

123

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SummaryDevelopment and standardization of fibrinolysis methods have progressed more slowly than coagulation testing and routine high‐throughput screening tests for fibrinolysis are still lacking. In laboratory research, a variety of approaches are available and are applied to understand the regulation of fibrinolysis and its contribution to the hemostatic balance. Fibrinolysis in normal blood is slow to develop. For practical purposes plasminogen activators can be added to clotting plasma, or euglobulin prepared to reduce endogenous inhibitors, but results are complicated by these manipulations. Observational studies to identify a ‘fibrinolysis deficit’ have concluded that excess fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI‐1) or thrombin‐activatable fibrinolysis inhibitor (TAFI), zymogen or active enzyme, may be associated with an increased risk of thrombosis. However, results are not always consistent and problems of adequate standardization are evident with these inhibitors and also for measurement of fibrin degradation products (D‐dimer). Few methods are available to investigate fibrinolysis under flow, or in whole blood, but viscoelastic methods (VMs) such as ROTEM and TEG do permit the contribution of cells, and importantly platelets, to be explored. VMs are used to diagnose clinical hyperfibrinolysis, which is associated with high mortality. There is a debate on the usefulness of VMs as a point‐of‐care test method, particularly in trauma. Despite the difficulties of many fibrinolysis methods, research on the fibrinolysis system, taking in wider interactions with hemostasis proteins, is progressing so that in future we may have more complete models and better diagnostic methods and therapeutics.

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Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy

Cited by 45 publications

References 32 publications

Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial

Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial

The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management

Measuring fibrinolysis: from research to routine diagnostic assays

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