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27/06/2016

Albumine plutôt que fibrinogène ?

Influences of limited resuscitation with plasma or plasma protein solutions on hemostasis and survival of rabbits with noncompressible hemorrhage

Kheirabadi BS et Al. J Trauma Acute Care Surg. 2016;81: 42–49

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Dans ce travail les auteurs évoquent la possibilité que les effets favorables d'une réanimation basée sur l'apport de plasma serait lié à l'apport de protéine et en particulier d'albumine qui aurait un effet tampon élevé, réduisant l'acidose métabolique, un des facteurs de la triade létale.

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BACKGROUND:

Plasma infusion with or without red blood cells is the current military standard of care for prehospital resuscitation of combat casualties. We examined possible advantages of early and limited resuscitation with fresh plasma compared with a single plasma protein or crystalloid solutions in an uncontrolled hemorrhage model in rabbits.

METHODS:

Anesthetized spontaneously breathing rabbits (3.3 ± 0.1 kg) were instrumented and subjected to a splenic uncontrolled hemorrhage. Rabbits in shock were resuscitated at 15 minutes with Plasma-Lyte (PAL; 30 mL/kg), PAL + fibrinogen (PAL + F; 30 mL + 100 mg/kg), fresh rabbit plasma (15 mL/kg), or 25% albumin (ALB; 5 mL/kg) solution, all given in two bolus intravenous injections (15 minutes apart) to achieve a mean arterial pressure of 65 mm Hg, n = 8 to 9/group. Animals were monitored for 2 hours or until death, and blood loss was measured. Blood samples and tissues were collected and analyzed.

RESULTS:

There were no differences among groups in baseline measures and their initial bleeding volume at 15 minutes. At 60 minutes after injury, mean arterial pressure was higher with ALB than with crystalloids (PAL or PAL + F), but shock indices were not different despite the large differences in resuscitation volumes. Fibrinogen addition to PAL only increased clot strength. Plasma resuscitation increased survival rate (75%) without significant improvement in coagulation measures. Albumin administration replenished total plasma protein and increased survival rate to 100% (p < .05 vs. crystalloids). No histological adverse events were identified in the vital organs.

alb25.jpg

CONCLUSIONS:

Fibrinogen administration added to a compatible crystalloid did not improve hemostatic outcomes. Plasma resuscitation increased survival rate; however, its effects did not differ from those obtained with 25% ALB at one-third of the volume. The ALB advantage was consistent with our previous findings in which 5% ALB was used at a volume equal to plasma. The benefit of plasma for resuscitation may be mostly due to its ALB content rather than its coagulation proteins

04/06/2016

PLyo: Une révolution ? Pas vraiment, une redécouverte

 Dried plasma: state of the science and recent developments

Pusateri AE et Al. Transfusion. 2016 Apr;56 Suppl 2:S128-39

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Les nouvelles modalités de transfusion mettent en avant le bénéfice de l'apport précoce de plasma. Les contraintes logistiques liées à l'emploi de plasma frais sont réelles. L'emploi  de plasma lyophilisé permet de raccourcir ce délai et peut représenter dans certaines conditions d'isolement la seule source disponibles de fractions coagulantes. Le plasma lyophylisé est un vieux monsieur, mais dont la place est fondamentale. Largement utilisé notamment par l'armée française pendant la guerre d'indocchine, le SSA a maintenu sa production jusqu'à ce que l'épidémie de VIH ne survienne. Depuis les années 1980, le SSA a travaillé sans relâche pour sécuriser un produit qui retrouve la place qui lui est due dans la  stratégie transfusionnelle du blessé de guerre (1)  Il s'agit donc d'une redécouverte avec un emploi effectif en opération dès 1996 (2), plutôt que de révolution. Le document proposé à la lecture fait le point sur cette historique et les développements à venir.  La lecture de ce document ne doit pas faire oublier la réflexion de plus en plus présente sur l'emploi  en situation d'isolement de l'intérêt de la transfusion de sang total, seule source de plaquettes, associé au recours à des fractions coagulantes comme le fibrinogène et les complexes prothrombiques. Une telle association représente probablement l'avenir de la réanimation hémostatique préhospitalière (3, 4).

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Historical dried plasma development Event Selected References

1930s Plasma lyophilization developed in the 1930s.

1940—Large scale production of pooled, lyophilized plasma by both the US and British established for war time use (to meet logistical constraints of whole blood and frozen/liquid plasma).ans les années

1941—Spray dried plasma produced for the Swedish Defense Department. 21 WWII Production 20-22 British produced >500,000 U lyophilized plasma during WWII. US produced >6,000,000 U lyophilized plasma during WWII. US/British distributed world-wide. Sweden produced approximately 17,000 U spray dried plasma for Sweden and Finland.

1945—Hepatitis 23 Hepatitis as a result of plasma transfusion recognized by the end of WWII. Believed that benefits outweighed the risk.

1945-1952—Hepatitis 24 Attempts at pathogen reduction and reducing pool size not successful. Several deaths in clinical studies of ultraviolet irradiated pooled plasma.

1953

—Department of the Army (Circular 73) directed that, because of the risk of serum hepatitis, the higher cost, and the need to use it for the production of specific globulins, plasma would not be used “to support blood volume” unless dextran was not available. 

—Serum albumin replaced plasma as primary resuscitative product for US Forces in Korea. 

1968—National Research Council Committee on Plasma and Plasma Substitutes recommended that “the use of whole, pooled human plasma be discouraged and even discontinued unless a clear cut case can be made for its unique requirements.” 

The French Military Blood Institute produced dried plasma from 1949 to 1984, and provided over 40,000 units to French military forces during the Indochina War. In 1985, production was discontinued due to risk of HIV infection.

Acide tranexaminique systématique: La roue tournerait-elle ?

Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients

Moore HB et Al. J Am Coll Surg. 2016 Apr;222(4):347-55. 

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La recommandation n°15 de la RFE Portant sur la réanimation du choc hémorragique stipule qu' il est recommandé d'administrer de l'acide tranexamique dès que possible chez les patients traumatisés à la dose de 1 g en bolus intraveineux en 10 min suivi de 1 g perfusé sur 8 h chez les patients traumatisés. Cette administration ne doit pas être initiée au delà de la 3e heure suivant la survenue d'un traumatisme avec choc hémorragique. Si l'étude CRASH-2 a montré que l'acide tranexamique réduisait significativement la mortalité. De nouvelles données disponibles depuis alimentent la discussion (1). Trois états du système de fibrinolyse peuvent être retrouvés: normal, hyperfibrinolyse, inhibition Les deux derniers sont associés à une surmortalité mais la fréquence des états d'inhibition de l'inhibition ne plaiderait pas pour une administration systématique mais ciblée d'exacyl. En qui nous concerne il faut à nouveau insister sur la précocité de l'administration d'exacyl dans l'heure chez les blessés sévères, pour lesquels le bénéfice en terme de mortalité est le plus grand (2). Une réflexion pour un emploi optimisé est en MARCHE (3, 4)

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BACKGROUND:

Fibrinolysis is a physiologic process that maintains microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis is associated with a doubling of mortality. Fibrinolysis shutdown, an acute impairment of fibrinolysis, has been recognized as a risk factor for increased mortality. The purpose of this study was to assess the incidence and outcomes of fibrinolysis phenotypes in 2 urban trauma centers.

STUDY DESIGN:

Injured patients included in the analysis were admitted between 2010 and 2013, were 18 years of age or older, and had an Injury Severity Score (ISS) > 15. Admission fibrinolysis phenotypes were determined by the clot lysis at 30 minutes (LY30): shutdown ≤ 0.8%, physiologic 0.9% to 2.9%, and hyperfibrinolysis ≥ 3%. Logistic regression was used to adjust for age, arrival blood pressure, ISS, mechanism, and facility.

RESULTS:

There were 2,540 patients who met inclusion criteria. Median age was 39 years (interquartile range [IQR] 26 to 55 years) and median ISS was 25 (IQR 20 to 33), with a mortality rate of 21%. Fibrinolysis shutdown was the most common phenotype (46%) followed by physiologic (36%) and hyperfibrinolysis (18%). Hyperfibrinolysis was associated with the highest death rate (34%), followed by shutdown (22%), and physiologic (14%, p < 0.001). The risk of mortality remained increased for hyperfibrinolysis (odds ratio [OR] 3.3, 95% CI 2.4 to 4.6, p < 0.0001) and shutdown (OR 1.6, 95% CI 1.3 to 2.1, p = 0.0003) compared with physiologic when adjusting for age, ISS, mechanism, head injury, and blood pressure (area under the receiver operating characteristics curve 0.82, 95% CI 0.80 to 0.84).

CONCLUSIONS:

Fibrinolysis shutdown is the most common phenotype on admission and is associated with increased mortality. These data provide additional evidence of distinct phenotypes of coagulation impairment and that individualized hemostatic therapy may be required.

  

 

| Tags : coagulopathie

03/06/2016

The 2015 Remote Damage Control Resuscitation Symposium

 

TRF_shadow_v2.jpg

Clic sur l'image pour accéder aux articles

 

11/04/2016

PROPPR Study: 1-1-2 aussi bien !

Damage-control resuscitation and emergency laparotomy: Findings from the PROPPR study

Undurraga VJ et AL. J Trauma Acute Care Surg. 2016 Apr;80(4):568-75

BACKGROUND:

The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage-controlresuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours compared with a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy.

METHODS:

Severely injured patients predicted to receive a massive transfusion admitted to 12 Level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomyas well as postsurgical survival at 24 hours and 30 days.

coagulopathie

RESULTS:

Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174 of 338) and 50.3% (172 of 342) for 1:1:1 and 1:1:2, respectively (p = 0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms; 24-hour survival was 86.8% (151 of 174) for 1:1:1 and 83.1% (143 of 172) for 1:1:2 (p = 0.29), and 30-day survival was 79.3% (138 of 174) for 1:1:1 and 75.0% (129 of 172) for 1:1:2 (p = 0.30).

CONCLUSION:

We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival.

28/01/2016

TXA: Interrogations

 Les études CRASH2 et MATTERS ont mis en évidence l'intérêt de l'emploi du TXA en traumatologie grave.

Il s'agit d'un dérivé de la lysine qui agit en se liant au plasminogène bloquant ainsi l'interaction plasminogène-fibrine, donc la fibrinolyse du caillot. Le TXA franchit la barrière sang-cerveau, diffuse dans le LCR et le globe oculaire

Persistent malgré tout quelques interrogations en matière d'innocuité persistent. Si l'étude crash2 n' pas montré de risque thromboembolique majeurs, ce n'est pas le cas d' l'étude MATTERS avec environ 10 fois plus d'épisodes thrombo-emboliques en cas d'usage de  TXA. Par ailleurs il est rapporté un risque d'hypotension lors de l'administration rapide de TXA et de convulsions lors de l'emploi de posologies élevées. Ceci ne remet pas en cause le recours précoce au TXA dont l'emploi ne doit pas être banalisé et respecter un certain nombre de règles: probabilité forte de coagulopathie traumatique notamment attesté par une hypotension sévère , 1ère dose le plus tôt possible (au mieux dans la première heure) et pas après 3h,  deuxième dose dans les 08h00, administration lente pour éviter hypotension, pas de surdosage facteur de crises convulsives, ne pas administrer en même temps/même ligne que du PLYO. 

Un certain nombre d'études complémentaires sont en cours:

1. L'étude  "Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage" a pour objectif d'affiner notre connaissance de l'emploi du TXA.

2.L'étude "Design of the Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) Trial: Addressing the Knowledge Gaps" a pour objet d'étuider la mortalité à 30 jours de traumatisés sévères pris en charge par medevac héliportées. 

3. L'étude "Tranexamic Acid Mechanisms and Pharmacokinetics In Traumatic Injury (TAMPITI Trial)"  vise quand à elle à confirmer un certain nombre d'hypothèses sur le mécanisme d'action.

Par ailleurs, le TXA n'est pas le seul antifibrinolyique utilisable.

 

Antifibrinolytic agents in current anaesthetic practice. Ortmann E. et Al. BJA 111 (4): 549–63 (2013).

Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg2012; 147: 113-119

Napolitano LM, Cohen MJ, Cotton BA, et al. Tranexamic acid in trauma: how should we use it? J Trauma Acute Care Surg 2013; 74: 1575-1586.

Pusateri AE, Weiskopf RB, Bebarta V, et al. Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities. Shock 2013; 39: 121-126

| Tags : coagulopathie

20/12/2015

Coagulopathie: Du fibrinogène avant tout

Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs

Nardi G et al. Critical Care (2015) 19:83

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Le damage control resuscitation fait largement appel à l'apport de plasma, concentrés de globules rouges et de plaquettes dans un rapport de 1/1/1 (1). Malgré la relative correction de la coagulopathie la survie à long terme ne semble pas être améliorée (2). Aussi certains proposent d'avoir plutôt recours à l'administration précoce de fibrinogène plutôt que l'administration de plasma. Le travail suivant qui propose l'apport précoce de  2g de fibrinogène est en faveur d'une telle démarche.

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INTRODUCTION:

Hemorrhage is the principal cause of death in the first few hours following severe injury. Coagulopathy is a frequent complication of critical bleeding. A network of Italian trauma centers recently developed a protocol to prevent and treat trauma-induced coagulopathy. A pre-post cohort multicenter study was conducted to assess the impact of the early coagulation support (ECS) protocol on blood products consumption,mortality and treatment costs.

METHODS:

We prospectively collected data from all severely injured patients (Injury Severity Score (ISS) >15) admitted to two trauma centers in 2013 and compared these findings with the data for 2011. Patients transfused with at least 3 units of packed red blood cells (PRBCs) within 24 hours of an accident were included in the study. In 2011, patients with significant hemorrhaging were treated with early administration of plasma with the aim of achieving a high (≥1:2) plasma-to-PRBC ratio. In 2013, the ECS protocol was the treatment strategy. Outcome data, blood product consumption and treatment costs were compared between the two periods.

RESULTS:

The two groups were well matched for demographics, injury severity (ISS: 32.9 in 2011 versus 33.6 in 2013) and clinical and laboratory data on admission. In 2013, a 40% overall reduction in PRBCs was observed, together with a 65% reduction in plasma and a 52% reduction in platelets. Patients in the ECS group received fewer blood products: 6.51 units of PRBCs versus 8.14 units. Plasma transfusions decreased from 8.98 units to 4.21 units (P <0.05), and platelets fell from 4.14 units to 2.53 units (P <0.05). Mortality in 2013 was 13.5% versus 20% in 2011 (13 versus 26 hospital deaths, respectively) (nonsignificant). When costs for blood components, factors and point-of-care tests were compared, a €76,340 saving in 2013 versus 2011 (23%) was recorded.

Coagulopathy2.jpg

CONCLUSIONS:

The introduction of the ECS protocol in two Italian trauma centers was associated with a marked reduction in blood product consumption, reaching statistical significance for plasma and platelets, and with a non-significant trend toward a reduction in early and 28-daymortality. The overall costs for transfusion and coagulation support (including point-of-care tests) decreased by 23% between 2011 and 2013.

| Tags : coagulopathie

12/11/2015

Et l'albumine ?

Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid? An experimental study in rabbits with parenchymal bleeding

Kheirabadi BS et Al. J Trauma Acute Care Surg. 2015;78: 752-759

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Il existe de grands débats sur la manière optimale d'assurer le remplissage vasculaire des blessés de guerre. Pour certains le fluide de référence est un hydroxyéthylamidon, pour d'autres un cristalloïde isotonique et en ce qui nous concerne les deux avec la mise en avant du sérum salé hypertonique premier suivi d'HEA. Actuellement il existe une tendance à promouvoir une autre stratégie faisant appel pour les blessés les plus graves au plasma voire la transfusion de sang frais. L'étude proposée avait pour objectif de confirmer l'intérêt d'une démarche "plasma premier". Une des surprises a été de constater que ce n'est pas cette dernière qui permettait d'obtenir le meilleur taux de survie mais l'emploi d'albumine, et ce de loin. Ces données expérimentales certes très partielles permettent aux auteurs (?)  de rediscuter les conclusions de travaux anciens notamment de l'étude SAFE (1,2). Les solutés d'albumine utilisés par cette dernière ont une osmolarité de 260 mosm/kg (versus 305 mosm/kg pour le sérum salé). Les effets délétères notamment chez le traumatisé crânien pourraient être dus non pas à  l'extravasation d'albumine dans le parenchyme cérébral lésé mais à l'hypoosmolarité de l'albumex 4%, ces deux mécanismes concourrant à la plus grande fréquence d'HTIC dans le groupe albumine (3).  A méditer

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BACKGROUND:

Reports of survival benefits of early transfusion of plasma with red blood cells (1:1 ratio) in trauma patients suggest that plasma may be a better fluid to replace Hextend for battlefield resuscitation. We studied possible advantages of prehospital resuscitation with plasma compared with Hextend or albumin in a model of uncontrolled hemorrhage.


METHODS:

Male New Zealand white rabbits (3.3 T 0.1 kg) were anesthetized, instrumented, and subjected to a splenic injury with uncontrolled bleeding. Ten minutes after injury (mean arterial pressure [MAP] G 40 mm Hg), the rabbits received small and equal volumes (15 mL/kg) of rabbit plasma (n = 10), Hextend (n = 10), or 5% human albumin (n = 9) or no fluid. Fluids were administered in two bolus injections (20 minutes apart) and targeted to aMAP of 65 mm Hg. Animals were monitored for 2.5 hours or until death, and their blood losses were measured. Arterial blood samples were collected at different times and analyzed for ABG, CBC, and coagulation tests.

RESULTS:

There were no differences in baseline measures among groups. Splenic injury caused similar hemorrhages (9.1 T 0.4 mL/kg at 10 minutes) and decreased MAP in all subjects. Subsequent resuscitation initiated additional bleeding. At 60 minutes after injury (20 minutes after resuscitation), longer activated partial thromboplastin time and lower fibrinogen concentrations were apparent compared with baseline values with differences among groups. Thrombelastography analysis indicated faster and stronger clot formation with plasma and albumin resuscitation than with Hextend use. Shock indices were increased in all groups, but smaller changes were measured in the albumin group. Total blood loss did not differ among resuscitated rabbits but was higher (p G 0.05) than among nonresuscitated animals. Survival rates were 11% (untreated), 40% (Hextend and plasma), and 89% (albumin, p G 0.05).

Albuminie COT.jpg

CONCLUSION:

Resuscitation with plasma or albumin better preserved coagulation function than did Hextend. However, despite these improvements, plasma resuscitation did not reduce blood loss or improve survival, while albumin administration seemed beneficial

10/11/2015

Dépakine chez le blessé cranien en choc ?

Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in alarge animal model of traumatic brain injury and hemorrhagic shock

Dekker SE et Al. J Surg Res. 2014 Jul;190(1):312-8

 

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Le concept du damaged control resuscitation fait appel en partie à de nouvelles modalités transfusionnelles et d'emploi de fractions coagulantes. D'autres approches sont possibles comme celles visant à restuarer la fonction plaquettaire. C'est ce que permettrait l'adminsitration de médicaments appartenant à la classe des inhibiteurs des histone deacetylase et dont les effets neuroprotecteurs pourraient ainsi être mis à profit.  Le document proposé semble conforter cette approche.

Documents reliés: 1, 2, 3

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BACKGROUND:

We have previously shown that resuscitation with fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) decreases the size of the brain lesion, and that addition of a histone deacetylase inhibitor, valproic acid (VPA), provides synergistic benefits. In this study, we hypothesized that VPA administration would be associated with a conservation of platelet function as measured by increased platelet activation after resuscitation.

MATERIALS AND METHODS:

Ten swine (42-50 kg) were subjected to TBI and HS (40% blood loss). Animals were left in shock for 2 h before resuscitation with either FFP or FFP+VPA (300 mg/kg). Serum levels of platelet activation markers transforming growth factor beta, CD40 L, P-selectin, and platelet endothelial cell adhesion molecule (PECAM) 1 were measured at baseline, postresuscitation, and after a 6-h observation period. Platelet activation markers were also measured in the brain whole cell lysates and immunohistochemistry.

RESULTS:

Circulating P-selectin levels were significantly higher in the FFP+VPA group compared with the FFP alone group (70.85±4.70 versus 48.44±7.28 ng/mL; P<0.01). Likewise, immunohistochemistry data showed elevated P-selectin in the VPA treatment group (22.30±10.39% versus 8.125±3.94%, P<0.01). Serum sCD40L levels were also higher in the FFP+VPA group (3.21±0.124 versus 2.38±0.124 ng/mL; P<0.01), as was brainsCD40L levels (1.41±0.15 versus 1.22±0.12 ng/mL; P=0.05). Circulating transforming growth factor beta levels were elevated in the FFP+VPA group, but this did not reach statistical significance (11.20±1.46 versus 8.09±1.41 ng/mL; P=0.17). Brain platelet endothelial cell adhesion molecule 1 levels were significantly lower in the FFP+VPA group compared with the FFP group (5.22±2.00 pg/mL versus 7.99±1.13 pg/mL; P=0.03).

CONCLUSIONS:

In this clinically relevant large animal model of combined TBI+HS, the addition of VPA to FFP resuscitation results in an early upregulation of platelet activation in the circulation and the brain. The previously observed neuroprotective effects of VPA may be due to a conservation of platelet function as measured by a higher platelet activation response after resuscitation.

| Tags : tbi, coagulopathie

09/11/2015

Plaie cérébrale et coagulopathie

Quelques faits

1. Elle est fréquente voire très fréquente: Greuters et al. Critical Care 2011 15:R2   doi:10.1186/cc9399

 

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2. Elle est + fréquente en cas d'hypoTA: Wafaisade  Neurocrit Care. 2010 Apr;12(2):211-9

COT TBI.jpg

3. Elle est de mauvais pronostic: J Emerg Trauma Shock. 2013 Jul-Sep; 6(3): 180–185

JETS-6-180-g002.jpg

4. Elle est mise en évidence plutôt par thromboélastographie (r TEG) : Sixta al., J Neurol Neurophysiol 2014, 6:5

rTEG TBI Coagulopathy.jpg

Un point plus complet

| Tags : coagulopathie

02/11/2015

Mg++: Médicament de la coagulopathie ?

Both acute delivery of and storage with magnesium sulfate promote cold-stored platelet aggregation and coagulation function

Meledeo MA et Al. J Trauma Acute Care Surg. 2015 Oct;79(4 Suppl 2):S139-45

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Il y a quelque mois était publié un travail de recherche portant sur  l'intérêt de l'administration de Adénosine/Lidocaïne/Mg2+ ALM (1, 2, 3). Une hypothèse faite par les auteurs  serait que L'ALM agirait comme un antifibrinolytique en activant la voie du thrombin-activatable fibrinolysis inhibitor (TAFI) plutôt que celle de la protéine C. Cette action passerait par un mécanisme antiinflammatoire, une modification de la polarité endothéliale et une action sur la fonction plaquettaire. Le travail expérimental dont l'abstract est présenté met en avant l'intérêt de l'adminsitration de magnésium pour la restauration de la fonction plaquettaire après conservation de palquettes d'aphérèse au delà de 5 jours. U

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BACKGROUND:

The platelet storage lesion causes loss of function and viability over time. A new paradigm for platelet storage is desired to enable safer, more effective transfusions while reducing waste. We hypothesized that repletion of Mg, which is chelated by citrate anticoagulant, could reduce platelet storage lesion severity when given in conjunction with storage at a refrigerated temperature.

METHODS:

Apheresis platelet units were collected from healthy donors and stored at 22°C or 4°C. On Days 0, 2, 4, and 8, samples were collected for analyses of receptor-mediated aggregation, coagulation, adhesion to collagen under flow, and viability. In the first series, samples were given anacute dose of MgSO4 before testing; in the second series, storage bags were supplemented with 0-, 3-, or 6-mM MgSO4.

RESULTS:

Acutely delivered MgSO4 induced a more rapid coagulation time in apheresis platelets, further enhanced by storage at 4°C. Plateletadhesion to a collagen surface while exposed to arterial shear rates (920 s) was enhanced by MgSO4 supplementation-acute MgSO4 had a large effect on adhesion of fresh platelets, which diminished more rapidly in 22°C samples, while storage with MgSO4 showed significant benefits even out to Day 4 at both temperatures. Although 4°C storage improves the longevity of platelet aggregation responses to agonists, MgSO4 supplementation did not change those responses.

CONCLUSION:

Acute MgSO4 reduces clot time likely through the transient increase of free Ca. Limited differences between platelet function inacute delivery of and storage with MgSO4 diminish the possibility that Mg-induced metabolic inhibition of platelets synergizes with 4°C storage. Regardless, magnesium supplementation to platelets is an exciting possibility in transfusion because the adhesion response of 22°C-stored platelets on Day 4 is significantly enhanced when stored with 6-mM MgSO4

| Tags : coagulopathie

23/10/2015

Quelle place pour les facteurs de la coagulation ?

PlaceFactCoag.jpg

Clic sur l'image pour suivre la conférence

18/09/2015

Coagulopathie traumatique: Mécanismes

Trauma-Induced Coagulopathy: An Institution's 35 Year Perspective on Practice and Research

Gonzales E. et Al. Scandinavian Journal of Surgery 103: 89–103, 2014

TraumaCoag.jpg

| Tags : coagulopathie

03/07/2015

Fibrinogène avec le TXA ?: Plutôt oui

Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury: Findings From the MATTERs II Study

Morrison JJ et Al. JAMA Surg. 2013;148(3):218-225.

 

Objective To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured.

Design Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality.

Setting A Role 3 Combat Surgical Hospital in southern Afghanistan.

Patients A total of 1332 patients were identified from prospectively collected UK and US trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758).

Main Outcome Measure In-hospital mortality.

Results Injury Severity Scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21).

Conclusions Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock.

 

| Tags : coagulopathie

27/03/2015

Hypersalé: Mieux avec de la lidocaïne , du magnésium et de l'adénosine ?

Correction of acute traumatic coagulopathy with small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ occurs within 5 minutes: A ROTEM analysis

Hayley L. et Al. J Trauma Acute Care Surg. 2015;78: 773-783

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La prévention/correction de la coagulopathie traumatique est un axe essentiel de la réanimation du traumatisé grave. Le choix du soluté a son importance. L'adjonction de lidocaïne, de magnésium et d'adénosine au NaCl7,5% serait bénéfique. On observerait une fibrinolyse beaucoup moins importante qu'avec le salé hypertonique seul.

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BACKGROUND: Acute traumatic coagulopathy is a major contributor to mortality and morbidity following hemorrhagic shock. Our aim was to examine the effect of small-volume 7.5% NaCl with adenosine, lidocaine, and Mg2+ (ALM) resuscitation on the timing of correction of coagulopathy in the rat model of severe hemorrhagic shock using ROTEM.

METHODS: Male rats (300Y450 g, n = 64) were randomly assigned to (1) baseline, (2) sham, (3) bleed, (4) shock, (5) 7.5% NaCl for 5 minutes, (6) 7.5% NaCl with ALM for 5 minutes, (7) 7.5% NaCl for 60 minutes, or (8) 7.5% NaCl with ALM for 60 minutes (all n = 8). For resuscitation, 0.3-mL intravenous bolus of 7.5% NaCl was administered with and without ALM (n = 8 each group). Hemodynamics and coagulopathy were assessed.

RESULTS: After hemorrhage, prothrombin time (PT) and activated partial thromboplastin time (aPTT) increased approximately four to six times, and ROTEM indicated hypocoagulopathy. After 60-minute shock, no sustainable clots could form. 7.5% NaCl increased mean arterial pressure (MAP) to 46 T 2 mm Hg at 5 minutes and generated a weak clot in EXTEM with hyperfibrinolysis in all tests. At 60 minutes, 7.5% NaCl failed to sustain MAP (43 T 5 mm Hg) and generate a viable clot. In direct contrast, 7.5% NaCl with ALM at 5 minutes resuscitatedMAP to 64 T 3 mm Hg, corrected PT and aPTT, and generated fully formed EXTEM and FIBTEM clots. At 60 minutes, MAP was 69 T 5 mm Hg, PT and aPTT were fully corrected, and > angle, clot amplitudes (A10, A30), as well as clot firmness and elasticity were not significantly different from baseline. ALM clot lysis at 60 minutes was significantly less than bleed, shock, or 7.5% NaCl, indicating protection against hyperfibrinolysis.

 

Soluté Miracle.jpg

CONCLUSION: Small-volume 7.5% NaCl failed to resuscitate and correct coagulopathy. In contrast, 7.5% NaCl with ALM resuscitated MAP and corrected coagulopathy at 5 minutes, with further improvements at 60 minutes in clot kinetics, propagation, and firmness. ALM fully reversed hyperfibrinolysis to baseline. The possible mechanisms are discussed. (J Trauma Acute Care Surg. 2015;78:

04/09/2014

Remplissage vasculaire: Evolution majeure du TCCC

Fluid Resuscitation for Hemorrhagic Shock in Tactical Combat Casualty Care
 

L'emploi préhospitalier de la transfusion de globules rouges et de plasma était évoqué de manière anecdotique. Une évolution importante survient dans la procédure américaine du TCCC (1, 2). Cette pratique est en passe de devenir une recommandation protocolée de théâtre pour les blessés en état de choc (Pas de pouls radial et conscience altérée el l'absence de traumatisme crânien)  hémorragique avec notons le recours au Plyo du CTSA.

" Tactical Field Care and TACEVAC Care

7. Fluid resuscitation

a. The resuscitation fluids of choice for casualties in hemorrhagic shock, listed from most to least preferred, are: whole blood*; plasma, RBCs and platelets in 1:1:1 ratio*; plasma and RBCs in 1:1 ratio; plasma or RBCs alone; Hextend; and crystalloid (Lactated Ringers or Plasma-Lyte A).

b. Assess for hemorrhagic shock (altered mental status in the absence of brain injury and/or weak or absent radial pulse).

1. If not in shock:

- No IV fluids are immediately necessary.

- Fluids by mouth are permissible if the casualty is conscious and can swallow.

2. If in shock and blood products are available under an approved command or theater blood product administration protocol:

- Resuscitate with whole blood*, or, if not available

- Plasma, RBCs and platelets in a 1:1:1 ratio*, or, if not available

- Plasma and RBCs in 1:1 ratio, or, if not available;

- Reconstituted dried plasma, liquid plasma or thawed plasma alone or RBCs alone;

- Reassess the casualty after each unit. Continue resuscitation until a palpable radial pulse, improved mental status or systolic BP of 80-90 mmHg is present.

3. If in shock and blood products are not available under an approved command or theater blood product administration protocol due to tactical or logistical constraints:

- Resuscitate with Hextend, or if not available;

- Lactated Ringers or Plasma-Lyte A;

- Reassess the casualty after each 500 mL IV bolus;

- Continue resuscitation until a palpable radial pulse, improved mental status, or systolic BP of 80-90 mmHg is present.

- Discontinue fluid administration when one or more of the

above end points has been achieved.

4. If a casualty with an altered mental status due to suspected TBI has a weak or absent peripheral pulse, resuscitate as necessary to restore and maintain a normal radial pulse. If BP monitoring is available, maintain a target systolic BP of at least 90 mmHg.

5. Reassess the casualty frequently to check for recurrence of shock. If shock recurs, recheck all external hemorrhage control measures to ensure that they are still effective and repeat the fluid resuscitation as outlined above.

* Neither whole blood nor apheresis platelets as these products are currently collected in theater are FDA-compliant. Consequently, whole blood and 1:1:1 resuscitation using apheresis platelets should be used only if all of the FDA-compliant blood products needed to support 1:1:1 resuscitation are not avalaible

21/11/2013

Le plasma lyophilisé: Bon pour le cerveau du traumatisé qui saigne

Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

Imam AM et Al. J Trauma Acute Care Surg. 2013;75: 976-983

accéder aux abstracts de la WTA publiés dans J trauma Acute care

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Bien sûr une étude animale, mais une de plus qui milite pour un emploi précoce du plasma lyophylisé.

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BACKGROUND: Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP.

METHODS:

Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tipimpactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced(40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm3) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured.

RESULTS:

This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly ( p G 0.05) decreased brain lesion size and swelling (51% and 54%, respectively).

LSP.jpg

CONCLUSION: In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages. 

| Tags : tbi, coagulopathie

07/08/2013

Plasma: En préhospitalier AUSSI +++

Point-of-injury use of reconstituted freeze dried plasma as a resuscitative fluid: A special report for prehospital trauma care

Glassberg E. et All. J J Trauma Acute Care Surg. 2013;75(Suppl 2):S111YS111.

La prise en charge d'hémorrragie catastrophique en phase préhospitalière est particulièrement complexe. Ces dernières années la mise en place d'un réseau structuré de prise en charge, 'application de procédures spécifiques visant à arrêter les hémorragies au plus tôt, le recours à l'acide tranexaminique, la prévention des hypothermies et l'application d'une politique raisonnée de rénaimation/chirurgie ont constitué une grande avancée. Certaines nations ont équipé leurs vecteurs d'évacuations de concentrés érythrocytaires. Le maintien d'une coagulation optimale est un enjeu majeur. Pour cela existe, entre autres,  le plasma lyophilisé. Les forces armées israéliennes militent pour l'emploi de ce type de solutions en phase préhospitalière

29/06/2013

Coagulopathie du trauma: Que faire ?

 Case Scenario: Management of Trauma-induced Coagulopathy in a Severe Blunt Trauma Patient

David JS et All. Anesthesiology 2013; 119:191–200 

CoagulopathieTrauma.jpeg

Un point très clair du problème

| Tags : coagulopathie

26/05/2013

Plasma lyophilisé: Une réalité

Le Service de Santé des Armées a recours depuis de nombreuses années (1, 2) à une présentation originale de plasma thérapeutique le PLYO.

Initialement réservé à un emploi en opérations extérieures, il vient d'être validé sous contraintes pour un usage sur le territoire national: Le plasma lyophilisé (PLYO) est principalement distribué aux unités médico-chirurgicales militaires déployées en Opérations Extérieures (OPEX) pour répondre aux contraintes logistiques du contexte opérationnel et à la nécessité de disposer,  sans délai, de plasma pour le traitement des blessés hémorragiques. En milieu civil, le PLYO pourrait être  utilisé par les établissements de santé présentant des difficultés logistiques majeures ne permettant pas  d’assurer une chaîne du froid négative ou au cours de situations d’extrême urgence avec nécessité d’un apport de plasma thérapeutique sans délai. Dans cette deuxième indication, le PLYO devrait être utilisé en  attendant que le plasma frais congelé soit décongelé et disponible. Le plasma lyophilisé français (PLyo®) préparé préférentiellement à partir de plasma frais congelé traité par l’amotosalen. Il est obtenu par lyophilisation à partir d’un mélange de PFC-IA issus d’aphérèse, provenant de dix donneurs différents au maximum, de groupes sanguins A, B, et AB, exempts d’anticorps immuns anti-A ou anti-B, conservés à une température inférieure ou égale à −25 °C.

Il en existe d'autres. Le plasma lyophilisé sud-africain (Bioplasma®) est le seul équivalent au monde du plasma lyophilisé français du fait de son universalité. Il s’agit d’un produit sud-africain bénéficiant d’une autorisation nationale depuis 1994 et commercialisé depuis 1996. Ce plasma est lyophilisé, universel et traité par solvant-détergent. Il existe en deux formats de flacon : 50 ou 200 mL. Le plasma lyophilisé allemand (LyoPlas N-W®), produit par le service de transfusion sanguine de la croix rouge allemande, provient d’un seul donneur de sang total ou d’aphérèse. Il n’est donc pas universel au regard de la compatibilité ABO. Le produit est sécurisé par quarantaine de quatre mois. Il peut être stocké 15 mois entre +2 et +25 °C.

Une révue récente fait le point sur les divers plasma thérapeutiques disponibles.

PlasmaTherap.jpeg

 


| Tags : coagulopathie