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      Evaluación in vitro de la eficacia de plaquetas convencionales, atemperadas y congeladas. Posible empleo en el medio militar Translated title: In vitro evaluation of the efficacy of fresh, temperatured and frozen platelets. Possible employment in the military environment

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          SUMMARY Introduction. Exsanguinating hemorrhage is the first preventable cause of death for combatants in armed conflicts, thus making the possibility of transfusing blood components early an absolutely essential benefit during health care for casualties generated in military operations. Throughout the numerous conflicts that have occurred during the past century, there have been important changes in the hemotherapy treatment of casualties along with an evolution of the health doctrine regarding this issue. In some massive transfusion protocols, the diagnostic technique of thromboelastometry (TE) has been used. TE is a test that shows the viscoelastic properties of blood from clot formation to fibrinolysis, evaluates platelet function and correlates quickly with the physiological process of hemostasis. The main objective of this study is the evaluation in vitro of the hemostatic capacity of the various cold, frozen and fresh platelet concentrates through standardized coagulation tests and thromboelastometry, clarifying whether the contribution to the clot is significantly improved with cold platelet pools (preserved at 4ºC), compared to fresh and frozen platelets. It is also intended to determine what advantages would be the incorporation of cold platelets in transfusion medicine performed in the military environment. Material and methods. An experimental study was designed to compare cold (refrigerated), frozen and fresh (conventional) platelets in vitro, analyzing their performance and effectiveness through systematic blood analysis, routine laboratory coagulation mechanisms (Prothrombin Time, Prothrombin Activity, Cephalin and Fibrinogen) and Rotational Thromboelastometry (ROTEM). A sample of 20 healthy patients was recruited, after informing them in writing and obtaining the mandatory informed consent, they donated 6 tubes with 10 ml citrate. of blood per patient. For the comparison, the data collected from the performance of the ROTEM between baseline and experimental samples (after platelet transfusion) were normally distributed and analyzed using the paired Student’s t-test and were analyzed by multiple linear regression, adjusting and not adjusting according to the platelet count. Approval was obtained from the Drug Research Ethics Committee and the hospital research committee. Results. The mean of the EXTEM CT parameter is significantly lower in the sample with frozen platelets compared to that of tempered and normal platelets. The mean of the EXTEM CFT parameter is significantly lower in the sample with normal platelets compared to that of frozen platelets. The mean of the EXTEM CFT parameter is significantly lower in the sample with frozen platelets compared to that of tempered platelets. The mean of the Platelet Index parameter is significantly higher in the sample with normal platelets compared to that of tempered platelets. The mean of the MCE PI parameter is significantly higher in the sample with tempered platelets compared to that of frozen platelets. Conclusion. After evaluating the hemostatic capacity in vitro using standardized coagulation tests and thromboelastometry, tempered platelets significantly improve the maximum elasticity of the clot in relation to platelet count compared to frozen platelets, but not compared to fresh platelets. The incorporation of tempered platelets in transfusion medicine in the military environment would be another treatment alternative for discharge with exsanguinating hemorrhage and would provide logistical advantages by increasing the shelf life of standard platelets from seven to twenty-one days and simplifying processing, transportation and Reconstitution of the blood component to the liquid medium as it is not necessary to freeze it.

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          Most cited references51

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          Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.

          Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. clinicaltrials.gov Identifier: NCT01545232.
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            Damage control resuscitation: directly addressing the early coagulopathy of trauma.

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              Mechanisms of platelet clearance and translation to improve platelet storage.

              Hundreds of billions of platelets are cleared daily from circulation via efficient and highly regulated mechanisms. These mechanisms may be stimulated by exogenous reagents or environmental changes to accelerate platelet clearance, leading to thrombocytopenia. The interplay between antiapoptotic Bcl-xL and proapoptotic molecules Bax and Bak sets an internal clock for the platelet lifespan, and BH3-only proteins, mitochondrial permeabilization, and phosphatidylserine (PS) exposure may also contribute to apoptosis-induced platelet clearance. Binding of plasma von Willebrand factor or antibodies to the ligand-binding domain of glycoprotein Ibα (GPIbα) on platelets can activate GPIb-IX in a shear-dependent manner by inducing unfolding of the mechanosensory domain therein, and trigger downstream signaling in the platelet including desialylation and PS exposure. Deglycosylated platelets are recognized by the Ashwell-Morell receptor and potentially other scavenger receptors, and are rapidly cleared by hepatocytes and/or macrophages. Inhibitors of platelet clearance pathways, including inhibitors of GPIbα shedding, neuraminidases, and platelet signaling, are efficacious at preserving the viability of platelets during storage and improving their recovery and survival in vivo. Overall, common mechanisms of platelet clearance have begun to emerge, suggesting potential strategies to extend the shelf-life of platelets stored at room temperature or to enable refrigerated storage.
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                Author and article information

                Journal
                sm
                Sanidad Militar
                Sanid. Mil.
                Ministerio de Defensa (Madrid, Madrid, Spain )
                1887-8571
                December 2022
                : 78
                : 4
                : 216-228
                Affiliations
                [7] Madrid Madrid orgnameUniversidad Europea de Madrid Spain
                [1] orgnameHospital Central de la Defensa Gómez Ulla orgdiv1Servicio de Hematología y Transfusión España
                [2] orgnameHospital Central de la Defensa Gómez Ulla orgdiv1Servicio de Anestesia y Reanimación España
                [6] Madrid orgnameUniversidad Politécnica de Madrid Spain
                [4] Madrid orgnameHospital Infanta Sofía orgdiv1Servicio de Anestesia y Reanimación España
                [5] Madrid orgnameUniversidad de Alcalá de Henares Spain
                [3] orgnameSpotLab España
                Article
                S1887-85712022000400004 S1887-8571(22)07800400004
                10.4321/s1887-85712022000400004
                50057759-c4a1-46fa-8af0-a8b9bc2d3a7f

                http://creativecommons.org/licenses/by/4.0/

                History
                : 25 November 2022
                : 30 November 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 52, Pages: 13
                Product

                SciELO Spain

                Categories
                Artículo Original

                platelets,platelet concentrates,frozen platelets,refrigerated platelets,cold platelets,platelet transfusion,platelet cryopreservation,whole blood,transfusion,military medicine,ROTEM,plaquetas,pool de plaquetas,plaquetas congeladas,plaquetas frías,plaquetas atemperadas,transfusión de plaquetas,criopreservación de plaquetas,sangre completa,transfusión,medicina militar

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