Evaluation of platelets componentized with the Reveos Automated Blood Processing System and stored for 7 days at room temperature in a non-Di(2-ethylhexyl) phthalate (DEHP) platelet pooling set.

BACKGROUND: Platelet concentrates (PCs) used for transfusion can be produced by apheresis or derived from whole blood (WB). The Reveos device is the first US Food and Drug Administration-approved automated blood processing system that can produce PCs. In this work, we evaluated the quality and function of Reveos-collected PCs stored for 7 days at room temperature. STUDY DESIGN AND METHODS: WB was collected from healthy donors and componentized on the day of collection (Fresh) or after an overnight hold (Overnight). PCs were produced (n = 7 Fresh; n = 6 Overnight), stored at room temperature in plasma, and evaluated on days 1 and 7 for quality metrics, platelet activation, clot formation, and aggregation response. RESULTS: Platelet count was comparable between Fresh and Overnight PCs. A drop in pH was reported in Fresh day 7 PCs (p < .001, vs. day 1) but not in Overnight. Overnight units displayed the lowest levels of P-selectin expression (p = .0008, vs. day 7 Fresh). Reduced clot strength and increased lysis were observed in both Fresh and Overnight units on day 7 (vs. day 1). Overnight-hold PCs resulted in the highest clot strength on day 7 (p = .0084, vs. Fresh). No differences in aggregation were reported between groups. CONCLUSION: Reveos-processed PCs produced from overnight-hold WB performed better in hemostatic function assays and displayed reduced activation compared to fresh WB-derived PCs, although both PC groups maintained platelet quality throughout storage. Utilization of overnight WB for PC preparation with Reveos holds promise as an alternative method of producing platelets for transfusion purposes.

Novel method for determining when a field-collected donor unit is sufficiently full.

BACKGROUND: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete. METHODS: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed. RESULTS: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g). CONCLUSION: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full.

A narrative review of prehospital hemorrhagic shock treatment with non-blood product medications.

BACKGROUND: Hemorrhagic shock remains a leading cause of death in both military and civilian trauma casualties. While standard of care involves blood product administration, maintaining normothermia, and restoring hemostatic function, alternative strategies to treat severe hemorrhage at or near the point of injury are needed. We reviewed adjunct solutions for managing severe hemorrhage in the prehospital environment. METHODS: We performed a literature review by searching PubMed with a combination of several keywords. Additional pertinent studies were identified by crossreferencing primary articles. Clinical experience of each author was also considered. RESULTS: We identified several promising antishock therapies that can be utilized in the prehospital setting: ethinyl estradiol sulfate (EES), polyethylene glycol 20,000 (PEG20K), C1 esterase inhibitors (e.g. Berinert, Cinryze), cyclosporin A, niacin, bortezomib, rosiglitazone, icatibant, diazoxide, and valproic acid (VPA). CONCLUSION: Several studies show promising adjunct treatment options in the management of severe prehospital hemorrhage. While some are rarely used, many others are readily available and commonly utilized for other indications. This suggests the potential for future use in resourcelimited settings. Human studies and case reports supporting their use are currently lacking.

Cold-stored platelets have better preserved contractile function in comparison with room temperature-stored platelets over 21 days.

Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.

More sophisticated than a drink cooler or an old sphygmomanometer but still not adequate for prehospital blood: A market review of commercially available equipment for prehospital blood transport and administration.

BACKGROUND: Hemorrhage is the leading cause of death in trauma patients with most fatalities occurring before reaching a higher level of care-this applies to both the civilian setting and the military combat setting. Hemostatic resuscitation with increased emphasis on blood transfusion while limiting use of crystalloids has become routine in trauma care. However, the prehospital setting-especially in combat-presents unique challenges with regard to storage, transport, and administration. We sought to evaluate available technology on the market for storage and administration technology that is relevant to the prehospital setting. STUDY DESIGN AND METHODS: We conducted a market review of available technology through subject-matter expert inquiry, reviews of published literature, reviews of Federal Drug Administration databases, internal military publications, and searches of Google. RESULTS: We reviewed and described a total of 103 blood transporters, 22 infusers, and 6 warmers. CONCLUSIONS: The risk of on-scene fatality in trauma patients and recent developments in trauma care demonstrate the need for prehospital transfusion. These transfusions have been logistically prohibited in many operations. We have reviewed the current commercially available equipment and recommended pursuit of equipment that improves accessibility to field transfusion. Current technology has limited applicability for the prehospital setting and is further limited for the military setting.

Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways.

BACKGROUND: Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold-stored platelets (CSPs) and RTPs after 5-day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days. STUDY DESIGN AND METHODS: This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial-associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics. RESULTS: CSP preserved mitochondria-associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro-apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs. CONCLUSION: Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well-documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients.

Evaluation of a lyophilized platelet-derived hemostatic product.

BACKGROUND: Current limitations of platelet shelf life to 5 days have led to an increasingly greater demand for hemostatic agents with greater longevity. The objective of this study was to evaluate the function of a lyophilized platelet-derived hemostatic product (thrombosome [TS]) as a potential alternative to fresh platelets. METHODS: Platelets were collected from whole blood from healthy donors. TSs were reconstituted with water and added to various configurations of reassembled whole blood (platelets, plasma, and RBCs); measures included rotational thromboelastometry (ROTEM), optical aggregometry, mitochondrial function, calibrated automated thrombogram, collagen adhesion under flow (shear flow assay), and flow cytometry. RESULTS: In ROTEM, no differences were observed between maximum clot formation values for contact pathway activation thromboelastometry tests with TSs or platelet samples. Significantly decreased aggregation was observed in the TSs versus platelets (p < 0.001 for all agonists). Flow cytometry measures demonstrated significant decreases in glycoprotein Ib expression and increases in phosphatidylserine expression in the TS group (p < 0.01). The calibrated automated thrombogram assay was suggestive (lag time and peak thrombin) that the TSs might have some thrombogenic properties. Measurements of mitochondrial function revealed that TSs had no functional mitochondria. CONCLUSION: In this study, TSs were shown to have nonfunctional mitochondria. ROTEM measures revealed that the TSs had no impact on clot strength. Likewise, compared to platelets, the TSs displayed minimal aggregation, had significantly more phosphatidylserine (measure of activation status), but had the ability to adhere to a collagen surface under flow conditions and contribute to clot formation and induced greater thrombin generation.

Prolyl hydroxylase domain inhibitor is an effective pre-hospital pharmaceutical intervention for trauma and hemorrhagic shock.

Pre-hospital potentially preventable trauma related deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock, acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 h following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.

Hemostatic Evaluation of Refrigerated Whole Blood Stored 7 Days Post-Expiration.

INTRODUCTION: The United States Army has shifted doctrine to focus on large-scale combat operations against peer to near-peer adversaries. Future conflicts could result in a limited supply chain, leaving medical providers with only expired blood products for treatment of hemorrhagic shock. This study evaluated quality, function, and safety metrics of whole blood stored for 1 week past regulated expiration (i.e., 35 days, in CPDA-1). MATERIALS AND METHODS: Whole blood units (n = 6) were collected in citrate phosphate dextrose adenine-1 (CPDA-1) anticoagulant and stored refrigerated for up to 42 days. Units were sampled on days 35, 37, 39, and 42 of storage and evaluated for the following: complete blood count, blood metabolism and chemistries, clotting dynamics, and presence of bacteria. RESULTS: The majority of evaluated parameters fell outside of normal clinical ranges beginning at day 35 of storage. At 42 days, blood pH was 6.58 ± 0.038, hemolysis was significantly increased (P = .037 vs day 35), and bacterial contamination was not evident. Glucose levels continuously dropped during extended storage. K+ was significantly increased at day 42 compared to day 35 (P = .010). A significant reduction in clot strength, factor V activity, and factor VIII activity was evident beginning at day 39 of storage. CONCLUSIONS: Storage of whole blood out to 42 days results in a continuous decline in function, but further in vivo safety studies should be performed to determine if the benefits of expired blood outweigh the risks. Other methods to safely extend storage of whole blood that maintain hemostatic function and preserve safety should be investigated, with emphasis placed on methods that reduce potassium leak and/or hemolysis.

In vitro evaluation of hyperosmotic canine plasma suitable for infusion.

OBJECTIVE: To determine the characteristics of canine freeze-dried plasma (cFDP) as it is serially diluted with sterile water. DESIGN: In vitro experimental study. SETTING: Government blood and coagulation research laboratory. ANIMALS: cFDP from a commercial manufacturer. INTERVENTIONS: Ten units of cFDP were reconstituted to 100%, 90%, 80%, 70%, 60%, 50%, and 40% of the recommended volume with sterile water. The resultant solutions were analyzed for coagulation factor activity (factors II, V, VII, VIII, IX, X, and XII as well as antithrombin), fibrinogen concentration, prothrombin time, activated partial thromboplastin time, viscosity, osmolality, and kaolin-activated thromboelastography. MEASUREMENTS AND MAIN RESULTS: Viscosity, osmolality, and turbidity properties of plasma were increased in a reconstitution volume-dependent manner, with the 40% suggested volume generating approximately 2-fold increases in each. Similarly, factor activity levels and fibrinogen concentration increased by approximately 2-fold over this range in a concentration-dependent manner. Prothrombin time declined from 11.4 seconds at 100% volume to 10.9 seconds at 70% before increasing to 11.9 seconds at 40%. Activated partial thromboplastin time increased exponentially from 21.8 seconds at 100% rehydration to 100.0 seconds at 40%. R-time on TEG increased from 3.1 to 13.9 minutes at 50% rehydration, while alpha angle declined from 61.3° to 24.7° over the same range, and the maximum amplitude initially increased from 13.2 mm at 100% water to 18.6 mm at 70% water before dropping back down to 14.6 mm at 50% water. No clotting was observed with 40% rehydration. CONCLUSIONS: The creation of hyperosmotic plasma from cFDP appears feasible with preservation of concentrated coagulation factors, although there are some unexplained effects that happen to coagulation functions at the highest concentrations tested using only 40%-50% of recommended rehydration volume. Further studies are needed to evaluate the hyperosmotic product in vivo.

The impact of delivery by a fixed-wing, sling-launched unmanned aerial vehicle on the hematologic function of whole blood.

BACKGROUND: Unmanned aerial vehicles (UAVs) have been shown to shorten delivery times of medical products in health care, providing a potential answer to the question of prehospital resuscitation where blood and blood products are not readily available. While the capabilities and efficiencies of delivery via UAVs are already well established, the postdelivery viability and hemostatic function of whole blood has not been examined. METHODS: Whole blood units were sampled for a preflight control and loaded onto a fixed wing UAV. The UAVs flew in predetermined flight paths to either deliver via parachute drop or direct recovery after UAV capture by arresting gear. Postflight and preflight samples were assayed for coagulation function with thromboelastography, blood chemistry, and free hemoglobin to observe hemolysis. RESULTS: No significant differences in any metric were observed between the blood samples assayed preflight versus those flown and parachute dropped or those flown and recovered from the UAV. CONCLUSION: The use of UAVs for delivery of whole blood offers significant benefits for prehospital care. Further innovations in UAV and transportation technologies will expand on an already strong foundation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

CAN POLYETHYLENE GLYCOL-20K REPLACE ALBUMIN FOR PREHOSPITAL TREATMENT OF HEMORRHAGIC SHOCK WHEN FULL RESUSCITATION IS UNAVAILABLE?

ABSTRACT: A solution of high concentration albumin has been used for temporal volume expansion when timely resuscitation was unavailable after hemorrhagic shock. However, during prolonged hemorrhagic shock, cell edema and interstitial dehydration can occur and impede the volume expansion effect of albumin. Polyethylene glycol-20K (PEG) can establish an osmotic gradient from swollen cells to capillary lumens and thus facilitate capillary fluid shift and volume expansion. We hypothesized that with similar osmolality, 7.5% PEG elicits more rapid and profound compensatory responses after hemorrhagic shock than 25% albumin. Rats were randomized into three groups (n = 8/group) based on treatment: saline (vehicle), PEG (7.5%), and albumin (25%). Trauma was induced in anesthetized rats with muscle injury and fibula fracture, followed by pressure-controlled hemorrhagic shock (MAP = 55 mm Hg) for 45 min. Animals then received an intravenous injection (0.3 mL/kg) of saline, PEG, or albumin. MAP, heart rate, blood gases, hematocrit, skeletal muscle capillary flow, renal blood flow, glomerular filtration rate, urinary flow, urinary sodium concentration, and mortality were monitored for another 2 hours. Polyethylene glycol-20K and albumin both improved MAP, renal and capillary blood flow, and renal oxygen delivery, and decreased hyperkalemia, hyperlactatemia, hematocrit, and mortality (saline: 100% PEG: 12.5%; albumin: 38%) over saline treatment. Compared with albumin, PEG had a more rapid decrease in hematocrit and more profound increases in MAP, diastolic pressure, renal blood flow, glomerular filtration rate, and urinary flow. These results suggest that PEG may be a better option than albumin for prolonged prehospital care of hemorrhagic shock.

Genetically engineered transfusable platelets using mRNA lipid nanoparticles.

Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.

A Scoping Review of Promising Alternative Blood Products for Prolonged Field Care.

Hemorrhage is the leading cause of potentially preventable death on the battlefield. Blood transfusions are used as treatment to restore circulating volume until the hemorrhage can be surgically controlled. Research has shown earlier transfusion of blood products has better casualty outcomes, so blood products have been pushed forward to the point of injury. Currently, there is a mixed use of blood components and whole blood in the prehospital setting-both of which have challenging supply chain requirements. Alternative blood products offer several potential advantages, as they are easier to mass produce, obviating the need for donor recruitment. They also have improved shelf-life stability, potentially remove cold-chain storage, and even cross-matching requirements. In this limited review, we sought to provide a narrative review of current promising developments including hemoglobin-based oxygen carriers, polyhemoglobin, platelet like cells, dried plasma, liquid plasma, fibrinogen concentrates, enzyme concentrates, nanoparticles, and perfluorocarbon-based artificial oxygen carriers.

Hemoglobin-Based Oxygen Carrier for the Reconstitution of Canine Freeze-Dried Plasma in an In Vitro Model of Resuscitation.

Military working dogs (MWDs) are force multipliers that are at risk for severe trauma when employed on the battlefield. When in severe hemorrhagic shock, MWDs require both oxygen- carrying capacity and replacement of vascular volume and coagulation factors. The objective of this study was to evaluate the hemostatic capacity of canine freeze-dried plasma (cFDP) with a Food and Drug Administration (FDA)-approved hemoglobin- based oxygen carrier (HBOC) in an in vitro model of resuscitation. Whole blood (WB) was collected from 10 MWDs, and these samples were diluted by 10%, 25%, or 40% with either cFDP (reconstituted with water), HBOC, cFDP (reconstituted with HBOC), or an equal volume of a 1:1 ratio of cFDP (reconstituted with water) and HBOC. Hemostatic parameters were minimally changed based on evaluation of prothrombin time, activated partial thromboplastin time, fibrinogen and thromboelastography at the 10% and 25% dilutions, and parameters consistent with a hypocoagulability were seen at dilutions of 40%. Based on the results of this study, additional research is warranted to determine if cFDP reconstituted with HBOC is a viable resuscitation product in canine trauma.

Incidence of Expired Blood Product Use in the US Central Command Theater of Operations.

OBJECTIVE: Introduction: During multi-domain combat operations, logistical constraints may compel forward medical personnel to decide whether to use expired blood products. The incidence of expired blood product usage in recent conflicts is unknown. METHODS: We queried the Armed Services Blood Program (ASBP) database of all blood administered in theater from 2002-2019. We categorized any administration of blood product with a transfusion date of 1-30 days after the expiration date for this analysis. We excluded any documented transfusions more than 30 days after the expiration date as likely represents clerical error based on study team experience. RESULTS: There were 1,491 (0.4% of the total transfusion dataset) units that met inclusion for this analysis. Of the 1,491, 86% (n=1,278 transfusions) will occur within 1-3 days post-expiration. These 1,491 units were transfused into 741 patients. The majority of expired blood product recipients were male (87%). Afghans were most frequent (46%), followed by US forces (22%) with most occurring during Operation Enduring Freedom (64%). Trauma was the most common mechanism of injury for these patients (70%). The most common blood type transfused to recipients was O positive (28%). The most frequently transfused expired unit was red blood cells (n=899), followed by platelets (n=299), followed by whole blood (n=152). CONCLUSIONS: Expired red blood cell and platelet use suggests a need for better methods for extending the lifespan of whole blood and further development of longer stability cold-stored platelets to meet the needs of our end-users. Our data arises from mature theaters during counterinsurgency operations. The incidence of transfusion of expired blood products may increase in future multi-domain operations where medical personnel are likely to operate under more resource constrained settings.

Toxicity of aluminum silicates used in hemostatic dressings toward human umbilical veins endothelial cells, HeLa cells, and RAW267.4 mouse macrophages.

BACKGROUND: Aluminum silicates have been used to control bleeding after severe traumatic injury. QuikClot (QC) was the first such product, and WoundStat (WS) is the most recent. We recently observed that WS caused vascular thrombosis when applied to stop bleeding. This study investigated the cellular toxicity of WS in different cell types that may be exposed to this mineral and compared the results with other minerals such as bentonite, kaolin, and QuikClot ACS+ (QC+). METHODS: Human umbilical vein endothelial cells (HUVEC), HeLa cells, and RAW267.4 mouse macrophage-like cells (RAW) were incubated directly with different concentrations of each mineral for 24 hours. Cell viability was determined metabolically using the AlamarBlue fluorescent technique. In another experiment, minerals were exposed to HUVEC via Transwell inserts with a polycarbonate filter (0.4-µm pore size) to prevent direct contact between cells and minerals for determining whether direct exposure or leaching compounds from minerals cause cytotoxicity. RESULTS: Incubation of HUVEC and RAW cells with 1 to 100 µg/mL of the minerals for 24 hours resulted in differential toxicities. The cytotoxicity of WS was equal to that of bentonite and higher than kaolin and QC+. Neither cell type survived for 24 hours in the presence of 100 µg/mL WS or bentonite. These minerals, however, had little effect on the viability of HeLa cells. In the second HUVEC experiment, a 10 times higher concentration of these compounds placed in Transwell inserts yielded no decrease in cell viability. This result indicates that leaching toxicants or binding of nutrients by the ion-exchange properties of minerals did not cause the toxicity. CONCLUSIONS: Although aluminum silicates seem relatively innocuous to epithelial cells, all produced some toxicity toward endothelial cells and macrophages. WS and bentonite were significantly more toxic than kaolin and zeolite present in QC+, respectively, at equivalent doses. The cytotoxic effect seemed to be caused by the direct contact of the minerals with the cells present in wounds. These data suggest that the future clearance of mineral-based hemostatic agents should require more extensive cytotoxicity testing than the current Food and Drug Administration requirements.

Effects of refrigerated storage on hemostatic stability of four canine plasma products.

OBJECTIVE: To assess clotting times, coagulation factor activities, sterility, and thromboelastographic parameters of liquid plasma (LP), thawed fresh frozen plasma (FFP-T), and 2 novel formulations of freeze-dried plasma (FDP) stored refrigerated over 35 days. SAMPLE: 6 units of canine LP and FFP-T from a commercial animal blood bank and 5 units each of 2 formulations of canine FDP. PROCEDURES: Prothrombin time; activated partial thromboplastin time; activities of coagulation factors II, V, VII, VIII, IX, X, XI, and XII; and thromboelastographic parameters were determined for each product on days 0 (baseline), 3, 7, 14, 21, 28, and 35. For each day, a sample of each product was also submitted for aerobic bacterial culture. RESULTS: Small changes in coagulation factor activities and mild increased time to initial clot formation in LP and FFP-T were noted over the 35-day storage period. Activities of factor VIII in FDP1 and factor XII in FDP2 were < 50% at baseline but varied throughout. Compared with FFP-T, time to initial clot formation was increased and clot strength was preserved or increased for the FDPs throughout the study. One FDP had decreased pH, compared with other products. No plasma product yielded bacterial growth. CONCLUSIONS AND CLINICAL RELEVANCE: Liquid plasma and FFP-T would be reasonable to use when stored refrigerated for up to 35 days. Both FDP products showed variability in coagulation factor activities. Studies investigating the usefulness of these plasma products (FDPs) in dogs and the variable days of refrigerated storage (all products) are warranted. (Am J Vet Res 2020;81:964-972).

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease.

Hematologic diseases include a broad range of acquired and congenital disorders, many of which affect plasma proteins that control hemostasis and immune responses. Therapeutic interventions for these disorders include transfusion of plasma, cryoprecipitate, immunoglobulins, or convalescent plasma-containing therapeutic antibodies from patients recovering from infectious diseases, as well as concentrated pro- or anticoagulant factors. This review will focus on recent advances in the uses of plasma and its derivatives for patients with acquired and congenital hematologic disorders.