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11/05/2018

Plasma lyophilisé: Utile et mieux que PFC ?

French lyophilized plasma versus fresh frozen plasma for the initial management of trauma-induced coagulopathy: a randomized open-label trial

Garrigue D et AL; J Thromb Haemost. 2018 Mar;16(3):481-489

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Le plasma lyophilisé retrouve d'évidence, en matière de réanimation transfusionnelle notamment celle du traumatisé,  toute la place qu'il avait perdu dans les années 1980. Son atout majeur est sa disponibilité qui permet un apport bien plus précoce que le PFC. Ce travail en montre tout l'intérêt. On peut néanmoins dans ce document se poser la question de la similarité des groupes étudiés et des critères d'évaluation de la coagulopathie ?

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Essentials

- An immediate supply of plasma in case of trauma-induced coagulopathy is required.

- The Traucc trial compared French Lyophilised Plasma (FLyP) and Fresh Frozen Plasma (FFP)

- FLyP achieved higher fibrinogen concentrations compared with FFP.

- FLyP led to a more rapid coagulopathy improvement than FFP.

Background

Guidelines recommend beginning hemostatic resuscitation immediately in trauma patients. We aimed to investigate if French lyophilized plasma (FLyP) was more effective than fresh frozen plasma (FFP) for the initial management of trauma-induced coagulopathy.

Methods In an open-label, phase 3, randomized trial (NCT02750150), we enrolled adult trauma patients requiring an emergency pack of 4 plasma units within 6 h of injury. We randomly assigned patients to receive 4-FLyP units or 4-FFP units. The primary endpoint was fibrinogen concentration at 45 min after randomization. Secondary outcomes included time to transfusion, changes in hemostatic parameters at different time-points, blood product requirements and 30-day in-hospital mortality.

Results

Forty-eight patients were randomized (FLyP, n = 24; FFP, n = 24). FLyP reduced the time from randomization to transfusion of first plasma unit compared with FFP (median[IQR],14[5-30] vs. 77[64-90] min). FLyP achieved a higher fibrinogen concentration 45 min after randomization compared with FFP (baseline-adjusted mean difference, 0.29 g L-1 ; 95% confidence interval [CI], 0.08-0.49) and a greater improvement in prothrombin time ratio, factor V and factor II. The between-group differences in coagulation parameters remained significant at 6 h. FLyP reduced fibrinogen concentrate requirements. Thirty-day in-hospital mortality rate was 22% with FLyP and 29% with FFP.

Conclusion FLyP led to a more rapid, pronounced and extended increase in fibrinogen concentrations and coagulopathy improvement compared with FFP in the initial management of trauma patients. FLyP represents an attractive option for trauma management, especially when facing logistical issues such as combat casualties or mass casualties related to terror attacks or disasters.

12/04/2018

Prélèvement de sang frais: VO2 Altérée

"Immediate effects of blood donation on physical and cognitive performance - A randomizedcontrolled double blinded trial"

 
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Il existe un engouement justifié pour la transfusion de sang frais en traumatologie de guerre. On peut faire remonter cette redécouverte au conflit bosniaque (1). Cependant voir en tout combattant un donneur potentiel est aller un peu vite en besogne. Ce travail, qui émane d'une équipe norvégienne pronant cette pratique (2) peut être interprété comme montrant une baisse de la VO2  de 6% associée à une altération certes non significative des fonctions cognitives. Il paraît dès lors un peu prématuré de vouloir généraliser cette pratique notamment au milieu des équipes intervenant en milieu très isolé, souvent en ayant été exposées à des contraintes physiologiques majeures et où les capacités physiques et cognitives doivent être maintenues. Ce n'est pas le cas de tous les combattants et certains sont certainement éligibles sous réserve du respect des règles d'hémovigilance de base (3).
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BACKGROUND:

The success of implementing Damage Control Resuscitation principles pre-hospital has been at the expense of several logistic burdens including the requirements for resupply, and the question of donor safety during the development of whole blood programs. Previous studies have reported effects on physical performance after blood donation, however none have investigated the effects of blooddonation on cognitive performance.

METHOD:

We describe a prospective double blindedrandomized controlled study comprised of a battery of tests: three cognitive tests, and VO2max testing on a cycle ergometer. Testing was performed 7 days before blinded donation (Baseline day), immediately after donation(Day 0), and 7 days (Day 7) after donation. The inclusion criteria included being active blood donors at the Haukeland University Hospital blood bank where eligibility requirements were met on the testing days and providing informed consent. Participants were randomized to either the experimental (n=26) or control group (n=31). Control group participants underwent a 'mock donation" in which a phlebotomy needle was placed but blood was not withdrawn.

RESULTS:

In the experimental group, mean VO2max declined 6% from 41.35 +/-1.7 /(min.kg) at baseline to 39.0 +/-1.6 /(min.kg) on Day 0, and increased to 40.51 +/-1.5 /(min.kg) on Day 7. Comparable values in the control group were 42.1 +/-1.8 /(min.kg) at baseline, 41.6 +/-1.8 /(min.kg) on Day 1 (1% decline from basline), and 41.8 +/-1.8 /(min.kg) on Day 7. Comparing scores of all three cognitive tests on Day 0 and Day 7 showed no significant differences, p>0.05.

CONCLUSION:

Our main findings are that executive cognitive and physical performance were well-maintained after whole blood donation in healthy blood donors. The findings inform post-donation guidance on when donors may be required to return to duty.

03/01/2018

Fibrinogène: En 1er chez les canadiens

Fibrinogen Concentrate in the Special Operations Forces Environment

Sanders S et al. Military Medecine, 00, 0/0:1, 2017

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Un choix raisonné et différent (Apport de 6 g de fibrinogène) des armées françaises qui s'intègre dans les nouvelles stratrégies transfusionnelles de prise en charge du blessé de guerre où la place de la transfusion de sang frais le fibrinogène et le plasma ont une place essentielle (1,2)

Aller sur le forum coagulopathie

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Introduction:

Hemorrhage is the most common cause of death among Special Operations Force (SOF) soldiers. Bringing remote damage control resuscitation into the far-forward combat environment is logistically challenging, as it requires blood products that generally require a robust cold chain. Alternatively, lyophilized products such as fibrinogen concentrate, which does not require thawing or blood group compatibility testing before use, might be advantageous in damage control resuscitation in the battlefield. In this report, we review the evidence for the use of fibrinogen concentrate in the Canadian SOF environment.

Materials and Methods:

The literature on the use of fibrinogen concentrate in the trauma setting was reviewed by Canadian Forces Services Working Group, in three separate meetings. Multiple stakeholders were consulted to obtain authoritative perspectives from subject matter experts on the use of fibrinogen concentrate in the Canadian SOF environment.

CanS b.png

We also conducted a comparison review of fibrinogen content, pathogen risk, shelf life, and methods required for use for fresh frozen plasma, cryoprecipitate, and fibrinogen concentrate relevant to their application in the far-forward combat environment.

Results:

Indications and a protocol for the use of fibrinogen as an adjunct to fresh whole blood were formulated based on a literature review and clinical expert opinion. Alternative strategies and other lyophilized blood products were considered before selecting fibrinogen concentrate as the lyophilized blood product of choice. Fibrinogen concentrate is an ABO-universal blood product with an excellent safety profile. Training was conducted by subject matter experts within civilian trauma centers and at military training facilities. The clinical efficacy and safety were confirmed by monitoring the use of fibrinogen concentrate in deployed combat settings.

Conclusion:

Fibrinogen concentrate is a useful adjunct to remote damage control resuscitation in the SOF environment. Fibrinogen concentrate was found to be robust for transport into the SOF environment and is widely accepted among SOF operators and medics

24/12/2017

AAST 2017: Utilité du TXA encore questionnée

Late TXA utilization is associated with Iincreased blood product transfusion: A secondary analysisof the pragmatic randomized optimal platelet and plasma ratios  (PROPPR) study

Aravind K. et AL . Session: XIIIA: Papers 45-54: Preclincial/Translational Science Paper 52

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Ce poster présenté au dernier AAST 2017 est une ré-interprétation de données de l'étude POPR. Il semblerait qu'au delà des premières heures l'administration précoce (dans la 1ère heure) de TXA n'améliore pas la survie à 24h et un mois. L'administration tardive (après la 1ère heure mais avant la 3ème) majorerait les besoins transfusionnels. Les auteurs de ce poster attirent l'attention sur la disparité des groupes comparés, ce qui peut expliquer leurs résultats.

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Introduction:

Exsanguination is the leading cause of preventable death after trauma. In addition to a balanced ratio blood component strategy, tranexamic acid (TXA) is used as an adjunct in hemorrhaging patients. This secondary analysis was performed to determine the incidence of TXA utilization and outcome in patients predicted to receive a massive transfusion (MT) in level 1 trauma centers.

Methods:

Trauma patients who were predicted to require a MT and admitted to 12 level I North American trauma centers were studied. Patients were divided into those who received TXA and those who did not. We examined 3 hour, 24 hour, and 30 day mortality. We also examined incidence of thromboembolic events, blood product administration within the first 24 hours, length of stay (hospital free days), ICU free days, as well as development of complications including acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), sepsis, and multisystem organ failure (MOF). In our multivariate analysis, we controlled for Injury Severity Score (ISS), Glasgow Coma Scale (GCS), treatment group, mechanism of injury, hypotension and/or tachycardia on admission, geriatric patient (age > 65), and site as independent variables.

Results:

137 out of 680 (20.1%) patients in the PROPPR study received TXA with 130 patients receiving TXA within the first 3 hours after admission. Other adjunctive therapies administered included cryoprecipitate (25.4%), and others (6.6%). The incidence of TXA administration did not differ between the ratio groups (50.3% vs 47.4%, p=0.55), but patients receiving TXA were more severely injured with a median ISS of 34(21) vs 26(20), p<0.01  and a lower median(IQR) GCS of 9(12) vs 14(12),  p<0.01. Multivariate linear regression analysis revealed no association between TXA administration and blood transfusion requirements (Table 1). Further analysis revealed that patients who received late (from >1 hour to ≤3 hours after arrival) TXA (41 patients) experienced increased blood requirements in the first 24 hours (Table 1) compared to those remaining 543 patients that did not receive TXA. There was no difference in blood product requirement in those patients who received TXA early (≤1 hour) (89 patients) versus those that did not receive TXA. In patients that receiv ed TXA, there was an increased incidence of ARDS(OR (95% CI) 1.99 (1.06,3.73), p=0.03), AKI (1.90 (1.13,3.20), p=0.01), and MOF (4.18 (1.52,11.48), p<0.01) even when controlling for the factors mentioned above. There was also a difference in adjusted 3 hour mortality (OR (95% CI) 0.22 (0.07,0.73), p=0.01) but not 24 hour (0.61 (0.30,1.24), p=0.18) or 30 day mortality (1.42 (0.78,2.59), p=0.25) for any TXA administration. There was no difference in adjusted thromboembolic events or adjusted length of stay. Subgroup analysis with additional variables that were found to have a difference between groups with a p​<0.20 were added to the regression model including hematocrit, platelet count, international normalized ratio, creatinine, lactate, and R value on thrombelastography. This analysis showed an increase in PRBC transfusion with late TXA administration (16 out of 232 patients, 7.51 (0.46,14.56), p=0.04), but showed no difference in FFP or platelet administration.

Conclusion: Early TXA use was not associated with improved outcomes. Late TXA use was associated with increased blood product resuscitation. TXA administration in general was associated with improved 3 hour mortality. This did not translate to an improvement in mortality at 24 hours or 30 days. There was a significant increase in the incidence of ARDS, AKI, and MOF in patients who received TXA but this analysis is limited by the differences in the 2 populations despite attempts to control for them

23/12/2017

Le glycoalyx: Une cible thérapeutique

Novel Adjunct Drugs Reverse Endothelial Glycocalyx Damage After Hemorrhagic Shock in Rats.
 
Torres Filho IP et Al. Shock. 2017 Nov;48(5):583-589
 

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La correction précoce de la coagulopathie traumatique est un des objectifs fondamentaux de la prise en charge du traumatisé sévère et en particulier des blessés de guerre. L'emploi de plasma lyophilisé / fibrinogène / fractions coagulantes concentrées et la transfusion de sang frais se fait selon des stratégies diverses visant à compenser les déficits observés (1) . La restauration d'une perméabilité capillaire est également une voie possible. On peut considérer que l'efficacité du plasma est en +/- grande partie liée à sa capacité à restaurer le glycocalyx endothélial (2). Le travail présenté est en faveur de l'emploi, à l'instar de l'acide tranexaminique pour la fibrinolyse, d'ajuvants pharmacologiques aux solutés de remplissage pour limiter l'atteinte du glycoclayx.

Allez sur le forum coagulopathie/transfusion

Mieux comprende le concept de perméabilité capillaire

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INTRODUCTION:

There is interest in the small-volume therapeutic use of adjunct drugs for treating hemorrhagic shock (HS). However, critical information is only partially available on mechanisms of action of promising compounds such as adenosine-lidocaine-magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M), and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx and hemodynamics.

METHODS:

After baseline, 40% of total blood volume was removed from 44 anesthetized Sprague-Dawley male rats. One hour after hemorrhage, animals were resuscitated using ALM, BHB/M, or P-188 followed by lactated Ringer's (LR, 15 mL/kg). Control animals were not treated (SHAM) or received LR alone. Sampled blood was used to quantify shed syndecan-1 in plasma; multiple systemic physiological parameters were recorded. In vivo glycocalyx thickness, microvascular permeability, and microhemodynamics were evaluated in >200 cremaster venules using intravital videomicroscopy.

RESULTS:

Compared with baseline, resuscitation using adjuncts was associated with glycocalyx restoration of 97 ± 9% (ALM), 75 ± 8% (BHB/M), and 85 ± 5% (P-188): significantly higher than LR-only (56 ± 4%). Significantly better permeability, similar to SHAM values, was measured after ALM and P-188, and low plasma syndecan-1 levels were measured after resuscitation with all adjuncts. Microhemodynamic changes were relatively small while systemic parameters such as mean arterial pressure and lactate improved but remained below or above the baseline, respectively, as expected from this hypotensive resuscitation model.

CONCLUSION:

The drugs ALM, BHB/M, and P-188 provide beneficial effects as adjuncts to hypotensive resuscitation in this HS model by mechanisms involving changes at the microvascular level including the glycocalyx.

21/12/2017

Pour du sang à l'avant: Le drone !

L'emploi du sang se heurte à de nombreux problèmes. Le recours à des drones n'est pas une utopie. Tout ceci est très étudié par les pays dont le maillage hospitaliers et les infrastructures sont peu développés. 

Les drones font partie du futur (1) et leur autonomie est un atout précieux pour qu’ils puissent devenir un moyen de porter rapidement secours aux individus. Ainsi, les aéronefs sont dès à présent envisagés comme une alternative pour livrer des équipements médicaux dans des lieux qui pourraient s’avérer plus compliqués à traverser pour l’être humain (2)

« Les drones pourraient être le meilleur système de livraison des équipements médicaux du vingt-et-unième siècle "

Diverses technologies de drone peuvent être employées. Un modèle tanzanien parait bien opérant  (3) et commence à être utilisé en routine au rwanda pour la délivrance de sang (4) . Certains ont démontré leur capacité à oeuvrer dans un rayon de 260 km (5, lire cette publication US). 

 

 

 

 

 

| Tags : drone

02/12/2017

Fibrinogène en PREMIER pour le trauma

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial.
 
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Cette étude est conduite dans un trauma center autrichien chez des traumatisés ayant un ISS >15 recevant soit des facteurs concentrés [fibrinogène +/- facteur XIII+/- PPSB ] soit du PFC suivis par thromboélastométrie. Un arrêt anticipé après analyse des 100 premiers patients est rapporté du fait d'un plus grand nombre de transfusions massives dans le groupe PFC. Cet article conclue sur la supériorité de la démarche facteurs concentrés. On notera la posologie initiale de 50 mg/kg de fibrinogène dans le groupe CFC pour un apport réel moyen de 8 g précoce alors que le groupe PFC reçoit  4 g fibrinogène plus tardivement en rescue. Ce travail insiste sur l'intérêt de l'apport PRECOCE, à posologie adhoc de fibrinogène.
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BACKGROUND:

Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure.

METHODS:

This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18-80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635.

FINDINGS:

Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis.

FIb premier.pngCFC premier.png

The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47-240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95-10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78-4·86], p=0·15).

INTERPRETATION:

Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP.

01/12/2017

Transfusion à l'avant: Surtout Plyo, et le sang ?

Early transfusion on battlefield before admission to role 2: A preliminary observational study during “Barkhane” operation in Sahel

Vitalys V. et Al. https://doi.org/10.1016/j.injury.2017.11.029

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Ce document rapporte essentiellement l'emploi de PLyo chez des blessés de guerre avant leur prise en charge en role 2. Beaucoup est écrit sur la faisabilité d'une telle pratique. On rappelle que l'emploi du plasma lyophilisé n'est pas une nouveauté y compris en milieu précaire (1). Le plasma lyophilisé était d'emploi très courant dans les années 70 et début 80, à un tel point qu'il était pratiquement utilisé comme soluté de remplissage chez le traumatisé routier grave. Il s'agit donc d'une redécouverte et on n'est  pas surpris que ceci puisse se retrouver 30 ans après avec un produit notoirement sécurisé (2).

Il est dommage que l'article ne détaille pas plus cet emploi au niveau des role 1 qui est le lieu de début de transfusion pour 5 des blessés transfusés sur 7, ce qui n'est pas vraiment mis en avant dans ce travail. La reconstitution du Plyo est simple, mais probablement moins aisée dans une voilure tournante que dans un Casanurse ou au sol. Cet article met également en avant l'absence de transfusion de sang total, ce qui est étonnant pour une pratique rentrée dans les moeurs chez nos collègues US et UK. Enfin on retrouve l'emploi de fibrinogène, dont l'apport suffisant ne peut être assuré par le PLyo seul, et que certains proposent en première ligne de fractions coagulantes (3). Chose intéressante deux échecs de reconstitution du Plyo ont été observées. 

Un article très intéressant, dont plusieurs auteurs sont en charge du développement du PLyo, avec dans la partie discussion un bon rappel des problématiques qui se posent dans de telles circonstances. Il est dommage que le regroupement des lésions du bassin avec l'atteinte des membres ait été fait car les problématiques de contrôle des hémorragies sont différentes. De même la description des lésions observées dans le groupe transfusé (qui ne sont pas tous porteurs d'un garrot), et l'analyse spécifique du groupe présentant une hémorragie encore active aurait été méritées.

Vers le forum coagulopathie

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Introduction

Haemorrage is the leading cause of death after combat related injuries and bleeding management is the cornerstone of management of these casualties. French armed forces are deployed in Barkhane operatio n in the Sahel-Saharan Strip who represents an immense area. Since this constraint implies evacuation times beyond doctrinal timelines, an institutional decision has been made to deploy blood products on the battlefield and transfuse casualties before role 2 admission if indicated. The purpose of this study was to evaluate the transfusion practices on battlefield during the first year following the implementation of this policy.

Materials and methods

prospective collection of data about combat related casualties categorized alpha evacuated to a role 2. Battlefield transfusion was defined as any transfusion of blood product (red blood cells, plasma, whole blood) performed by role 1 or Medevac team before admission at a role 2. Patients’ characteristics, battlefield transfusions’ characteristics and complications were analysed.

Results

During the one year study, a total of 29 alpha casualties were included during the period study. Twenty-eight could be analysed, 7/28 (25%) being transfused on battlefield, representing a total of 22 transfusion episodes. The most frequently blood product transfused was French lyophilized plasma (FLYP). Most of transfusion episodes occurred during medevac. Compared to non-battlefield transfused casualties, battlefield transfused casualties suffered more wounded anatomical regions (median number of 3 versus 2, p = 0.04), had a higher injury severity score (median ISS of 45 versus 25, p = 0,01) and were more often transfused at role 2, received more plasma units and whole blood units. There was no difference in evacuation time to role 2 between patients transfused on battlefield and non-transfused patients. There was no complication related to battlefield transfusions. Blood products transfusion onset on battlefield ranged from 75 min to 192 min after injury.

Conclusion

Battlefield transfusion for combat-related casualties is a logistical challenge. Our study showed that such a program is feasible even in an extended area as Sahel-Saharan Strip operation theatre and reduces time to first blood product transfusion for alpha casualties. FLYP is the first line blood product on the battlefield

| Tags : transfusion

31/08/2017

TXA: Peut être pas si évident

Military use of TXA in combat trauma: Does it matter?

Howard JT et Al Trauma Acute Care Surg. 2017 Jun 9. doi: 10.1097/TA.0000000000001613. [Epub ahead of print]
 

BACKGROUND:

Tranexamic acid (TXA) has been previously reported to have a mortality benefit in civilian and combat-related trauma, and was thus added to the Joint Theater Trauma System Damage Control Resuscitation Clinical Practice Guideline. As part of ongoing system-wide performance improvement, the use of TXA has been closely monitored. The goal was to evaluate the efficacy and safety of TXA use in military casualties and provide additional guidance for continued use.

METHODS:

A total of 3,773 casualties were included in this retrospective, observational study of data gathered from a trauma registry. The total sample, along with 3 sub-samples for massive transfusion patients (n=784), propensity-matched sample (n=1,030) and US/NATO military (n=1,262), were assessed for administration of TXA and time from injury to administration of TXA. Outcomes included mortality and occurrence of pulmonary embolism (PE) and deep vein thrombosis (DVT). Multivariable proportional hazards regression models with robust standard error estimates were used to estimate hazard ratios (HR) for assessment of outcomes while controlling for covariates.

RESULTS:

Results of univariate and multivariate analyses of the total sample (HR=0.97; 95%CI 0.62-1.53; p=0.86); massive transfusion sample (HR=0.84; 95%CI 0.46-1.56; p=0.51); propensity-matched sample (HR=0.68; 95%CI 0.27-1.73; p=0.34); and US/NATO military sample (HR=0.76; 95%CI 0.30-1.92; p=0.48) indicate no statistically significant association between TXA use and mortality. Use of TXA was associated with increased risk of PE in the total sample (HR=2.82; 95%CI 2.08-3.81; p<0.001); massive transfusion sample (HR=3.64; 95%CI 1.96-6.78; p=0.003); US/NATO military sample (HR=2.55; 95%CI 1.73-3.69; p=0.002); but not the propensity-matched sample (HR=3.36; 95%CI 0.80-14.10; p=0.10). TXA was also associated with increased risk of DVT in the total sample (HR=2.00; 95%CI 1.21-3.30; p=0.02) and US/NATO military sample (HR=2.18; 95%CI 1.20-3.96; p=0.02).

CONCLUSIONS:

In the largest study on TXA use in a combat trauma population, TXA was not significantly associated with mortality, due to lack of statistical power. However, our HR estimates for mortality among patients who received TXA are consistent with previous findings from the CRASH2 trial. At the same time, continued scrutiny and surveillance of TXA use in military trauma, specifically for prevention of thromboembolic events, is warranted.

| Tags : transfusion

29/07/2017

Fibrinogène ET Plasma

Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma.

 

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Un travail qui est en faveur de l'association de fibrinogène et de plasma pour la prise en charge des hémorragies massives. Dans le contexte militaire, une stratégie basée sur l'apport initial du fibrinogène puis du Plyo apparaît censé (1). Lire les reco européennes.

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Massive traumatic haemorrhage is aggravated through the development of trauma-induced coagulopathy, which is managed by plasma transfusion and/or fibrinogen concentrate administration. It is yet unclear whether these treatments are equally potent in ensuring adequate haemostasis, and whether additional factor XIII (FXIII) administration provides further benefits.

In this study, we compared ROTEM whole blood coagulation profiles after experimental massive transfusion with different transfusion regimens in an in vitro model of dilution- and transfusion-related coagulopathy. Healthy donor blood was mixed 1 + 1 with six different transfusion regimens. Each regimen contained RBC, platelet concentrate, and either fresh frozen plasma (FFP) or Ringer's acetate (RA). The regimens were further augmented through addition of a low- or medium-dose fibrinogen concentrate and FXIII.

Transfusion with FFP alone was insufficient to maintain tissue-factor activated clot strength, coincidental with a deficiency in fibrin-based clot strength. Fibrinogen concentrate conserved, but did not improve coagulation kinetics and overall clot strength. Only combination therapy with FFP and low-dose fibrinogen concentrate improved both coagulation kinetics and fibrin-based clot strength. Administration of FXIII did not result in an improvement of clot strength. In conclusion, combination therapy with both FFP and low-dose fibrinogen concentrate improved clotting time and produced firm clots, representing a possible preferred first-line regimen to manage trauma-induced coagulopathy when RBC and platelets are also transfused. Further research is required to identify optimal first-line transfusion fluids for massive traumatic haemorrhage.

| Tags : coagulopathie

14/06/2017

Albumine préhospitalière: Idée qui fait son chemin

Albumin for Prehospital Fluid Resuscitation of Hemorrhagic Shock in Tactical Combat Casualty Care

 

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Une publication récente de Kheirabadi BS et Al. (1) évoque l'intérêt potentiel de l'albumine concentrée, notammment son pouvoir tampon important, pour la prise en charge de l'hémorragie, usage qu'il ne faut pas confondre avec celui de l'albumine à 4% dont l'emploi reste controversé (2) après l'étude SAFE (3). Lire ce point (5)

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Optimal fluid resuscitation on the battlefield in the absence of blood products remains unclear. Contemporary Combat medics are generally limited to hydroxyethyl starch or crystalloid solutions, both of which present significant drawbacks. Obtaining US Food and Drug Administration (FDA)-approved freeze-dried plasma (FDP) is a top casualty care research priority for the US Military. Interest in this agent reflects a desire to simultaneously expand intravascular volume and address coagulopathy. The history of FDP dates to the Second World War, when American expeditionary forces used this agent frequently. Also fielded was 25% albumin, an agent that lacks coagulation factors but offers impressive volume expansion with minimal weight to carry and requires no reconstitution in the field. The current potential value of 25% albumin is largely overlooked. Although FDP presents an attractive future option for battlefield prehospital fluid resuscitation once FDA approved, this article argues that in the interim, 25% albumin, augmented with fibrinogen concentrate and tranexamic acid to mitigate hemodilution effects on coagulation capacity, offers an effective volume resuscitation alternative that could save lives on the battlefield 

| Tags : hémorragie

05/05/2017

Fractions coagulantes en er mieux que PFC

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial.

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Un travail dont les conclusions sont très claires. La prise en charge de la coagulopathie traumatique bénéficie bien plus d'une stratégie d'apports ciblés de fractions coagulantes concentrées, notamment de fibrinogène ici 50 mg/kg, qu'une stratégie classique basée sur l'apport de PFC. 

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Background 

Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure.

Methods

This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18–80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635.

Findings

Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis. The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47–240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95–10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78–4·86], p=0·15).

Interpretation

Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP.

 

| Tags : coagulopathie

02/02/2017

Coagulopathie: Une affaire personnelle

Individual clotting factor contributions to mortality following trauma.

 

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Un travail intéressant qui portant sur 1463 traumatisés d'ISS médian de 16 et qui met en avant l'existence de deux profils de coagulopathie traumatique (16% des patients pris en charge). Dans 49,30 des cas, un premier est en rapport avec des anomalies des facteurs II,VII,IX,X et protéine C . Le second profil (17% des patients) exprime des anomalies sur les facteurs V et VIII. Seuls seraient liés à une motralité à 28j. LA déplétion en facteur V serait associée à une mortalité à long terme. Ce travail milite pour une approche personnalisée de la ocaguklopathie traumatique.

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BACKGROUND:

Acute traumatic coagulopathy affects 20% to 30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aimed to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma.

METHODS:

This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between February 2005 and February 2015. Factors II, V, VII, VIII, IX, and X and protein C activity on admission and mortality status at 28 days were assessed. Predictors of 28-day mortality in univariate analysis were included in multiple logistic regression controlling for traumatic brain injury (TBI), acidosis, age, and mechanism of injury. Principal component analysis was utilized to identify phenotypic coagulation.

RESULTS:

Complete coagulation factor data were available for 876 (61%) of 1,429 patients. In multiple logistic regression, factors V (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.76-0.97), VIII (OR, 0.97; 95% CI, 0.95-0.99), and X (OR, 0.79; 95% CI, 0.68-0.92) and protein C (OR, 1.17; 95% CI, 1.05-1.30) significantly predicted 28-day mortality after controlling for age, base deficit, mechanism of injury, and TBI. Principal component analysis identified two significant principal components (Phenotypes 1 and 2) that accounted for 66.3% of the total variance. Phenotype 1 (factors II, VII, IX, and X and protein C abnormalities) explained 49.3% and was associated with increased injury, coagulopathy, TBI, and mortality. Phenotype 2 (factors V and VIII abnormalities) explained 17.0% and was associated with increased coagulopathy, blunt injury, and mortality. Only Phenotype 2 remained significantly associated with 28-day mortality in multiple logistic regression.

CONCLUSIONS:

Principal component analysis identified two distinct phenotypes within the entirety of global clotting factor abnormalities, and these findings substantiate the crucial association of factors V and VIII on mortality following trauma. This may be the first step toward identifying unique phenotypes after injury and personalizing hemostatic resuscitation.

22/01/2017

Du sang qui descend du ciel

Nous ne sommes pas les seuls à avoir à faire face au contexte d'isolement. Il est particulièrement intéressant de regarder comment ces problèmes sont abordés par les pays en voie de construction. L'exemple rwandais devrait nous interpeller. Le recours à des drones de livraison en contexte militaire n'est pas une utopie car ce mode de ravitaillement a été utilisé en afghanistan.

 



| Tags : transfusion

21/01/2017

Coagulopathie: Fibrinogène avant PLyo, mais les 2 et + tôt ?

Tactical damage control resuscitation in austere military environments.
 
 
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Un sujet très débattu. Mais il semble bien que l'apport de fibrinogène doive être envisagé très précocément, en association au PLyo dont les caractéristiques poids/volume/concentration ne sont pas optimales pour toutes les situations de combat débarqué. En effet l'apport précoce d'au moins 3g  de fibrinogène ne peut pas être assuré par un PLYO (il en faut au moins 6). Ce niveau de supplémentation pourrait être approché par un flacon de fibrinogène, lors de la phase de combat débarqué, suivi par un ou deux PLYo qui peut être pensé pendant la phase de MEDEVAC. Une telle approche est conforme aux recommandations européennes en la matière (1). Une autre voie, de recherche, est de recourir à des PLyo plus concentrés (2,3), des plaquettes lyophylisées (4,5), ou des solutés spécifiques (6). On rapelle qu' l'intérêt du PLyo ne se limite pas à l'apport de fractions coagulantes mais aussi à l'apport d'un ensemble de substrats notamment protéique qui améliore la dysfonction endothéliale traumatique (7).
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Despite the early uses of tourniquets and haemostatic dressings, blood loss still accounts for the vast majority of preventable deaths on the battlefield. Over the last few years, progress has been made in the management of such injuries, especially with the use of damage control resuscitation concepts. The early application of these procedures, on the field, may constitute the best opportunity to improve survival from combat injury during remote operations.

DATA SOURCES:

Currently available literature relating to trauma-induced coagulopathy treatment and far-forward transfusion was identified by searches of electronic databases. The level of evidence and methodology of the research were reviewed for each article. The appropriateness for field utilisation of each medication was then discussed to take into account the characteristics of remote military operations.

CONCLUSIONS:

In tactical situations, in association with haemostatic procedures (tourniquet, suture, etc), tranexamic acid should be the first medication used according to the current guidelines. The use of fibrinogen concentrate should also be considered for patients in haemorrhagic shock, especially if point-of-care (POC) testing of haemostasis or shock severity is available. If POC evaluation is not available, it seems reasonable to still administer this treatment after clinical assessment, particularly if the evacuation is delayed. In this situation, lyophilised plasma may also be given as a resuscitation fluid while respecting permissive hypotension. Whole blood transfusion in the field deserves special attention.

coagulopathie,transfusion

In addition to the aforementioned treatments, if the field care is prolonged, whole blood transfusion must be considered if it does not delay the evacuation

08/01/2017

Albumine: Bon pour la coagulopathie ?

Does small-volume resuscitation with crystalloids or colloids influence hemostasis and survival of rabbits subjected to lethal uncontrolled hemorrhage?

 
 
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Une publication qui complète celle publiée (ici) par la même équipe sur l'intérêt de l'albumine concentrée.
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BACKGROUND:

Prehospital, small-volume resuscitation of combat casualties with a synthetic colloid (6% hydroxyethyl starch [HES] 670/0.75) has been recommended when blood or blood components are unavailable. We studied hemostatic effects of a newer synthetic colloid (6% HES, 130/0.4) compared with either a natural colloid (albumin) or to crystalloids in an uncontrolled hemorrhage model.

METHODS:

Spontaneously breathing New Zealand white rabbits (3.4 ± 0.1 kg) were anesthetized, instrumented, and subjected to a splenic injury with uncontrolled bleeding. Fifteen minutes after injury, rabbits were in shock (mean arterial pressure [MAP] = 26 ± 1.3 mm Hg, and received colloids (6% HES, 130/0.4 or 5% albumin at 15 mL/kg), or crystalloids (normal saline at 30 mL/kg or 5% hypertonic saline at 7.5 mL/kg) for resuscitation in two intravenous bolus injections (15 minutes apart) to raise their MAP to 65 mm Hg, n = 9/group. Animals were monitored for 2.5 hours or until death, and blood losses were measured. Blood samples were analyzed for arterial blood gas, complete blood count, and coagulation measures.

RESULTS:

There were no differences among groups in baseline measures and initial hemorrhage volume (11.9 ± 0.6 mL/kg) at 15 minutes postinjury. Twenty minutes after fluid resuscitation (1 hour postinjury), MAP was higher, shock indices were lower, and blood pH was higher in colloids versus crystalloids groups (p < 0.05). Administration of 6% HES 130/0.4 colloid produced the largest hemodilution (54% decrease in hematocrit, p < 0.05 vs. hypertonic saline). Activated partial thromboplastin time increased approximately 35% above baseline in all groups except in 6% HES 130/0.4 group in which it doubled. Clot strength was reduced (15%) only in the 6% HES 130/0.4 group. 6% HES 130/0.4 resuscitation produced the largest blood loss and 33% survival rate that was not different than the crystalloid groups. Albumin produced the best hemostatic and survival outcomes (78%).

CONCLUSION:

Small-volume resuscitation with crystalloids appeared inadequate to treat hypovolemic shock and prevent death. 6% HES 130/0.4 was effective hemodynamically but detrimental to hemostasis. Albumin produced the best outcomes consistent with our previous observations. Further studies are needed to prove benefit of albumin solution as a possible resuscitation fluid for treating combat casualties at the point of injury.

Synopsis of the updated European trauma guideline

Management of trauma-induced coagulopathy (TIC): a synopsis of the updated European trauma guideline

Maegele M. J Res Hosp 2016;1:27

Uncontrolled hemorrhage and trauma-induced coagulopathy (TIC) are still the major causes for preventable death after trauma .

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Approximately one out of four severely injured trauma patients admitted to the hospital is bleeding with variable degrees of laboratory coagulopathy. Meanwhile, TIC is recognized as an own clinical entity with substantial impact on outcome and survival after trauma. There has been speculation about the potential mechanisms underlying TIC but much of the data continues to be rather correlative than causative with robust links still lacking.

02/01/2017

Plyo: En intraosseux aussi

Pre-hospital intra-osseous freeze dried plasma transfusion: a case report

Rottenstreich et al. Disaster and Military Medicine 2015, 1:8

Background: Hemorrhage and coagulopathy are among the leading causes of death in combat and are considered the leading causes of preventable deaths. Plasma, in the form of Fresh Frozen Plasma (FFP) is considered a key component in the Damage Control Resuscitation performed within hospitals. Freeze-Dried Plasma (FDP) can be stored at room temperature and therefore is potentially useful in pre-hospital conditions. Our case report join to few cases where FDP was administered at the point of injury. It is also unique as it describes an intra- osseous administration given to pediatric patient.

Case report: M.S. otherwise healthy 13 year old girl was injured due to gunshots and grenade blast. On the first triage by the IDF medical teams she suffered from: Severe hemorrhagic shock, (Blood pressure could not be measured, Heart rate 163), superficial wounds to her face, (forehead and Rt. Eye), gunshot wounds with active bleeding from her Lt. Arm and her RT. Knee (Mangled Extremity Severity Score (MESS) 8) and open fractures of left elbow and right thigh. A peripheral intravenous catheter was established and 1 g tranexamic acid in 500 ml of Hartman fluid were administered. Due to difficulties in establishing a functioning intra-venous line, an intra-osseous catheter was established and one unit of FDP (250 ml) was given in the field. She was transferred by a military medical team to a regional civilian hospital for further treatment. Upon arrival to the hospital her blood pressure and heart rate were significantly improved. After three weeks of hospitalization M.S. was discharged and she was returned to her homeland.

Conclusion: We have described the successful use of FDP for pre hospital resuscitation of a 13 year old girl suffering from severe hemorrhagic shock as a result of gunshots and grenade blast. This case report demonstrates that intra-osseous FDP administration for as part pre hospital resuscitation of children has a favorable outcome.

| Tags : intraosseux

Coagulopathy/ Eléments de compréhension

Advances in the understanding of trauma-induced coagulopathy

Chang R. et al Blood. 2016;128(8):1043-1049

 

Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratorybased evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be “normal” after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.

| Tags : coagulopathie

19/12/2016

The 2015 Remote Damage Control Resuscitation Symposium

Transfusion.jpg

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