Dried Plasma for Major Trauma: Past, Present, and Future.

Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well.

Ultrafast gelling bioadhesive based on blood plasma and gelatin for wound closure and healing.

Tissue adhesives offer a plethora of advantages in achieving efficient wound closure over conventional sutures and staples. Such materials are of great value, especially in cases where suturing could potentially damage tissues or compromise blood flow or in cases of hard-to-reach areas. Besides providing wound closure, the tissue adhesives must also facilitate wound healing. Previously, plasma-based tissue adhesives and similar bioinspired strategies have been utilized to aid in wound healing. Still, their application is constrained by factors such as high cost, diminished biocompatibility, prolonged gelation times, inadequate swelling, quick resorption, as well as short-term and inconsistent efficacy. To address these limitations, we report the development of a highly biocompatible and ultrafast-gelling tissue adhesive hydrogels. Freeze-dried platelet-rich plasma, heat-denatured freeze-dried platelet-poor plasma, and gelatin were utilized as the base matrix. Gelation was initiated by adding tetrakis hydroxymethyl phosphonium chloride. The fabricated gels displayed rapid gelation (3-4 s), low swelling, increased proliferation, and migration against L929 cells and had porcine skin tissue adhesion strength similar to that of plasma-based commercial glue (Tisseel®).

Association of freeze-dried plasma with 24-h mortality among trauma patients at risk for hemorrhage.

BACKGROUND: Blood products form the cornerstone of contemporary hemorrhage control but are limited resources. Freeze-dried plasma (FDP), which contains coagulation factors, is a promising adjunct in hemostatic resuscitation. We explore the association between FDP alone or in combination with other blood products on 24-h mortality. STUDY DESIGN AND METHODS: This is a secondary data analysis from a cross-sectional prospective observational multicenter study of adult trauma patients in the Western Cape of South Africa. We compare mortality among trauma patients at risk of hemorrhage in three treatment groups: Blood Products only, FDP + Blood Products, and FDP only. We apply inverse probability of treatment weighting and fit a multivariable Cox proportional hazards model to assess the hazard of 24-h mortality. RESULTS: Four hundred and forty-eight patients were included, and 55 (12.2%) died within 24 h of hospital arrival. Compared to the Blood Products only group, we found no difference in 24-h mortality for the FDP + Blood Product group (p = .40) and a lower hazard of death for the FDP only group (hazard = 0.38; 95% CI, 0.15-1.00; p = .05). However, sensitivity analyses showed no difference in 24-h mortality across treatments in subgroups with moderate and severe shock, early blood product administration, and accounting for immortal time bias. CONCLUSION: We found insufficient evidence to conclude there is a difference in relative 24-h mortality among trauma patients at risk for hemorrhage who received FDP alone, blood products alone, or blood products with FDP. There may be an adjunctive role for FDP in hemorrhagic shock resuscitation in settings with significantly restricted access to blood products.

Post-Reconstitution Hemostatic Stability Profiles of Canadian and German Freeze-Dried Plasma.

Despite the importance of the hemostatic properties of reconstituted freeze-dried plasma (FDP) for trauma resuscitation, few studies have been conducted to determine its post-reconstitution hemostatic stability. This study aimed to assess the short- (≤24 h) and long-term (≥168 h) hemostatic stabilities of Canadian and German freeze-dried plasma (CFDP and LyoPlas) after reconstitution and storage under different conditions. Post-reconstitution hemostatic profiles were determined using rotational thromboelastometry (ROTEM) and a Stago analyzer, as both are widely used as standard methods for assessing the quality of plasma. When compared to the initial reconstituted CFDP, there were no changes in ROTEM measurements for INTEM maximum clot firmness (MCF), EXTEM clotting time (CT) and MCF, and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), D-dimer concentration, plasminogen, and protein C activities after storage at 4 °C for 24 h and room temperature (RT) (22-25 °C) for 4 h. However, an increase in INTEM CT and decreases in fibrinogen concentration, factors V and VIII, and protein S activities were observed after storage at 4 °C for 24 h, while an increase in factor V and decreases in antithrombin and protein S activities were seen after storage at RT for 4 h. Evaluation of the long-term stability of reconstituted LyoPlas showed decreased stability in both global and specific hemostatic profiles with increasing storage temperatures, particularly at 35 °C, where progressive changes in CT and MCF, PT, PTT, fibrinogen concentration, factor V, antithrombin, protein C, and protein S activities were seen even after storage for 4 h. We confirmed the short-term stability of CFDP in global hemostatic properties after reconstitution and storage at RT, consistent with the shelf life of reconstituted LyoPlas. The long-term stability analyses suggest that the post-reconstitution hemostatic stability of FDP products would decrease over time with increasing storage temperature, with a significant loss of hemostatic functions at 35 °C compared to 22 °C or below. Therefore, the shelf life of reconstituted FDP should be recommended according to the storage temperature.

Past meets present: Reviving 80-year-old Canadian dried serum from World War II and its significance in advancing modern freeze-dried plasma for prehospital management of haemorrhage.

During World War II, Charles H. Best utilized Charles R. Drew's plasma isolation and drying technique to lead Canada's initiative to provide dried serum as a means of primary resuscitation for British casualties on the frontlines. Serum was likely utilized over plasma for its volume expansion properties without the risk of clotting during prolonged storage. We reconstituted dried serum from 1943 and discovered intact albumin, as well as anti-thrombin, plasminogen, protein C and protein S activity. Proteomic analysis identified 71 proteins, most prominent being albumin, and positive for hepatitis B by serological testing. Transmission of blood-borne diseases ended the programme, until modern advances in testing and pathogen reduction revived this technology. We tested the latest iteration of Canadian freeze-dried plasma (FDP), which was stored for 4 years, and demonstrated that its clotting capacity remained equivalent to fresh frozen plasma. We recommend that FDP is a strong alternative to contemporary prehospital resuscitation fluids (e.g. normal saline/lactated Ringer's) in managing prehospital haemorrhage where whole blood is unavailable.

Prehospital Freeze-Dried Plasma in Trauma: A Critical Review.

Major traumatic hemorrhage is now frequently treated by early hemostatic resuscitation on hospital arrival. Prehospital hemostatic resuscitation could therefore improve outcomes for bleeding trauma patients, but there are logistical challenges. Freeze-dried plasma (FDP) offers indisputable logistical advantages over conventional blood products, such as long shelf life, stability at ambient temperature, and rapid reconstitution without specialized equipment. We sought high level, randomized, controlled evidence of FDP clinical efficacy in trauma. A structured systematic search of MEDLINE/PubMed was carried out and identified 52 relevant English language publications. Three studies involving 607 patients met our criteria: Resuscitation with Blood Products in Patients with Trauma-related Hemorrhagic Shock receiving Prehospital Care (RePHILL, n = 501); Prehospital Lyophilized Plasma Transfusion for Trauma-Induced Coagulopathy in Patients at Risk for Hemorrhagic Shock (PREHO-PLYO, n = 150); and a pilot Australian trial (n = 25). RePHILL found no effect of FDP plus packed red blood cells (PRBC) concentrate transfusion versus saline on mortality. PREHO-PLYO found no effect of FDP versus saline on International Normalized Ratio (INR) at hospital arrival. The pilot trial found that study of PRBC versus PRBC plus FDP was feasible during long air transport times to an Australian trauma centre. Further research is required to determine under what conditions FDP might provide prehospital benefit to trauma patients.

Blood products and its applications for the treatment of military trauma and diseases / 军事医学

The first blood product albumin was developed during World War Ⅱ.Since then, blood products began to play an irreplaceable role in military trauma and emergency cares .Currently, the supporting system of blood and blood products has become increasingly sophisticated .Development of novel blood products also improved dramatically .Universal virus inactivated freeze-dried plasma has also been purchased by the military .Albumin is used as antishock blood volume expansion for emergency treatment of military trauma .Different kinds of albumin including albumin of various concentra-tions, high purity albumin and albumin in soft packages are available .Specific immunoglobulin has become the regular stra-tegic storage of some developed countries , used for the prevention and treatment of infection in military trauma , emerging infectious diseases and against the potential threat of bioagents and bioterrorism .Local hemostatic produced upon fibrinogen and thrombin as well as coagulator Factor Ⅶperforming integral hemostasis effect have become increasingly significant for treating hemorrhage in military trauma .Development of anticoagulants including human protein C and antithrombin has got great improvement .These medicines have the potential for preventing and treating sepsis caused by military trauma .Prote-ase inhibitors including α2-macroglobulin are expected to work in the specific medicine .In conclusion , blood products will play a greater role in the future war and non war military operations .