Plasma: indications, controversies, and opportunities.

Plasma is overused as a blood product worldwide; however, data supporting appropriate use of plasma is scant. Its most common utilization is for treatment of coagulopathy in actively bleeding patients; it is also used for coagulation optimization prior to procedures with specific coagulation profile targets. A baseline literature review in PUBMED and Google Scholar was done (1 January 2000 to 1 June 2023), utilizing the following search terms: plasma, fresh frozen plasma, lyophilized plasma, indications, massive transfusion protocol, liver disease, warfarin reversal, cardiothoracic surgery, INR < 2. An initial review of the titles and abstracts excluded all articles that were not focused on transfusional medicine. Additional references were obtained from citations within the retrieved articles. This narrative review discusses the main indications for appropriate plasma use, mainly coagulation factor replacement, major hemorrhage protocol, coagulopathy in liver disease, bleeding in the setting of vitamin K antagonists, among others. The correlation between concentration of coagulation factors and INR, as well as the proper plasma dosing with its volume being weight-based, is also discussed. A high value approach to plasma utilization is supported with a review of the clinical situations where plasma is overutilized or unnecessary. Finally, a discussion of novel plasma products is presented for enhanced awareness.

Multi-center Retrospective Study of Factors Affecting Perioperative Transfusion of Packed Red Blood Cells for Pelvic Fracture Patients.

OBJECTIVE: To analyze the use of packed red blood cells (PRBCs) for patients with pelvic fracture and evaluate factors associated with PRBC transfusion for patients with pelvic fracture. METHODS: This retrospective cohort study collected 551 patients with pelvic fractures from six hospitals between September 1, 2012, and June 31, 2019. The age span of patients varied from 10 to 95 years old, and they were classified into two groups based on high-energy pelvic fractures (HE-PFs) or low-energy pelvic fractures (LE-PFs). The study's outcome was the use of PRBCs, fresh frozen plasma (FFP), and albumin. Demographic data, characteristics, laboratory tests, clinical treatment details, and clinical outcomes were compared between the two groups. Factors that were statistically associated with perioperative PRBCs in univariate analyses were included to conduct an optimal scale regression to determine the independent factors for perioperative PRBCs. RESULTS: A total of 551 patients were screened from six hospitals, and after inclusion and exclusion, 319 were finally included and finished the follow-up from admission to discharge, while four patients died during hospitalization. Three hundred and nineteen patients were classified into two groups by their injury mechanisms. A total of 230/319 (72.1%) patients were classified into the HE-PF group, and 89/319 (27.8%) patients were classified into the LE-PF group. Patients in the HE-PF group were transfused with 4.5 (3-8) units of PRBCs, 300 (0-600) ml of FFP, and 0 (0-30) g of albumin, while patients in the LE-PF group were transfused with 3.5 (2-4.5) units of PRBCs, 0 (0-295) ml of FFP, and 0 (0-0) g of albumin (all P < 0.001). There were higher proportions of male patients and patients under 65 in the HE-PF group (all P < 0.001). HE-PF group patients were more severely injured and likely to take external fixation. The optimal scale regression revealed four significant factors associated with perioperative transfused PRBCs, which were patients on admission with hemorrhagic shock (importance = 0.283, P = 0.004), followed by fracture types identified by Tile classification (importance = 0.156, P < 0.001), hemoglobin levels below 70 g/L on admission (importance = 0.283, P = 0.004), followed by fracture types identified by Tile classification (importance = 0.156, P < 0.001), hemoglobin levels below 70 g/L on admission (importance = 0.148, P = 0.039), and methods of pelvic fixation (importance = 0.008, P = 0.026), ranked by the importance. CONCLUSION: Patients with HE-PFs had increased transfusions of PRBCs, FFP, and albumin, and hemorrhagic shock on admission, Tile classification, Hb levels, and stabilization methods were found to be associated with perioperative PRBCs.

Thrombelastography and transfusion patterns in severely injured pediatric trauma patients with blunt solid organ injuries.

BACKGROUND: Thrombelastography (TEG) has emerged as a useful tool to diagnose coagulopathy and guide blood product usage during trauma resuscitations. This study sought to evaluate the correlation between TEG-directed blood product administration in severely injured pediatric trauma patients with blunt solid organ injuries (BSOIs). METHODS: Patients (≤18 years) with severe BSOIs who presented as highest-level trauma activations at two pediatric trauma centers were included. Thrombelastography results were evaluated to determine indications for blood product administration and rates of TEG-directed resuscitation. Tetrachoric correlations and regression modeling were used to correlate TEG-directed resuscitation with clinical outcomes. RESULTS: Of 64 patients who met the inclusion criteria, 32.8% (21) had elevated R times and 23.4% (15) had shortened α angles. Maximum amplitude was shortened in 29.7% (19), and percent clot lysis 30 minutes after maximum amplitude that is >3% was seen in 17.0% (9). Thrombelastography-directed resuscitation of fresh frozen plasma was followed 54.7% of the time compared with 67.2% and 81.2% for platelets and cryoprecipitate, respectively. Thrombelastography-directed resuscitation with platelets (odds ratio, 0.56; 95% confidence interval, 0.33-0.93; p = 0.03) and/or cryoprecipitate (odds ratio, 0.09; 95% confidence interval, 0.01-0.42, p = 0.003) were associated with decreased hospital length of stay and mortality, respectively. CONCLUSION: Severely injured pediatric trauma patients with BSOIs were often coagulopathic upon presentation to the emergency department. Thrombelastography-directed resuscitation with platelets and/or cryoprecipitate was followed for the majority of patients and was associated with improved outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management, level III.

Guideline development for prevention of transfusion-associated graft-versus-host disease: reduction of indications for irradiated blood components after prestorage leukodepletion of blood components.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, commonly fatal complication of transfusion preventable by irradiation of blood units. The revision of the Dutch transfusion guideline addressed the question whether irradiation is still necessary if blood components are prestorage leukodepleted. We searched for published cases of TA-GVHD following transfusion of prestorage leukodepleted blood and through contacting haemovigilance systems. Six presumed cases were found, dating from 1998 to 2013. Four out of six patients had received one or more non-irradiated units despite recognised indications for irradiated blood components. In the countries providing information, over 50 million prestorage leukodepleted, non-irradiated, non-pathogen-reduced cellular components were transfused in a 10-year period. Potential benefits of lifting indications for irradiation were considered. These include reduced irradiation costs (€ 1.5 million annually in the Netherlands) and less donor exposure for neonates. Findings were presented in an invitational expert meeting. Recommendations linked to human leukocyte antigen similarity between donor and recipient or intra-uterine transfusion were left unchanged. Indications linked to long-lasting deep T-cell suppression were defined with durations of 6 or 12 months after end of treatment (e.g. autologous or allogeneic stem cell transplantation). Need for continued alertness to TA-GVHD and haemovigilance reporting of erroneous non-irradiated transfusions was emphasised.

Dose-dependent association between blood transfusion and nosocomial infections in trauma patients: A secondary analysis of patients from the PAMPer trial.

BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a survival benefit to trauma patients who received thawed plasma as part of early resuscitation. The objective of our study was to examine the association between blood transfusion and nosocomial infections among trauma patients who participated in the PAMPer trial. We hypothesized that transfusion of blood products will be associated with the development of nosocomial infections in a dose-dependent fashion. METHODS: We performed a secondary analysis of prospectively collected data of patients in the PAMPer trial with hospital length of stay of at least 3 days. Demographics, injury characteristics, and number of blood products transfused were obtained to evaluate outcomes. Bivariate analysis was performed to identify differences between patients with and without nosocomial infections. Two logistic regression models were created to evaluate the association between nosocomial infections and (1) any transfusion of blood products, and (2) quantity of blood products. Both models were adjusted for age, sex, and Injury Severity Score. RESULTS: A total of 399 patients were included: age, 46 years (interquartile range, 29-59 years); Injury Severity Score, 22 (interquartile range, 12-29); 73% male; 80% blunt mechanism; and 40 (10%) deaths. Ninety-three (27%) developed nosocomial infections, including pneumonia (n = 67), bloodstream infections (n = 14), catheter-associated urinary tract infection (n = 10), skin and soft tissue infection (n = 8), Clostridium difficile colitis (n = 7), empyema (n = 6), and complicated intra-abdominal infections (n = 3). Nearly 80% (n = 307) of patients received packed red blood cells (PRBCs); 12% received cryoprecipitate, 69% received plasma, and 27% received platelets. Patients who received any PRBCs had more than a twofold increase in nosocomial infections (odds ratio, 2.15; 95% confidence interval, 1.01-4.58; p = 0.047). The number of PRBCs given was also associated with the development of nosocomial infection (odds ratio, 1.10; 95% confidence interval, 1.05-1.16; p < 0.001). CONCLUSION: Trauma patients in the PAMPer trial who received a transfusion of at least 1 U of PRBCs incurred a twofold increased risk of nosocomial infection, and the risk of infection was dose dependent. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Outcome measures used in clinical research evaluating prehospital blood component transfusion in traumatically injured bleeding patients: A systematic review.

BACKGROUND: Trial outcomes should be relevant to all stakeholders and allow assessment of interventions' efficacy and safety at appropriate timeframes. There is no consensus regarding outcome measures in the growing field of prehospital trauma transfusion research. Harmonization of future clinical outcome reporting is key to facilitate interstudy comparisons and generate cohesive, robust evidence to guide practice. The objective of this study was to evaluate outcome measures reported in prehospital trauma transfusion trials. METHODS: Data Sources, Eligibility Criteria, Participants, and InterventionsWe conducted a scoping systematic review to identify the type, number, and definitions of outcomes reported in randomized controlled trials, and prospective and retrospective observational cohort studies investigating prehospital blood component transfusion in adult and pediatric patients with traumatic hemorrhage. Electronic database searching of PubMed, Embase, Web of Science, Cochrane, OVID, clinical trials.gov, and the Transfusion Evidence Library was completed in accordance with Preferred Reporting Items for Meta-analyses guidelines.Study Appraisal and Synthesis MethodsTwo review authors independently extracted outcome data. Unique lists of salutogenic (patient-reported health and wellbeing outcomes) and nonsalutogenic focused outcomes were established. RESULTS: A total of 3,471 records were identified. Thirty-four studies fulfilled the inclusion criteria: 4 military (n = 1,566 patients) and 30 civilian (n = 14,398 patients), all between 2000 and 2020. Two hundred twelve individual non-patient-reported outcomes were identified, which collapsed into 20 outcome domains with varied definitions and timings. All primary outcomes measured effectiveness, rather than safety or complications. Sixty-nine percent reported mortality, with 11 different definitions. No salutogenic outcomes were reported. CONCLUSION: There is heterogeneity in outcome reporting and definitions, an absence of patient-reported outcome, and an emphasis on clinical effectiveness rather than safety or adverse events in prehospital trauma transfusion trials. We recommend stakeholder consultation and a Delphi process to develop a clearly defined minimum core outcome set for prehospital trauma transfusion trials. LEVEL OF EVIDENCE: Scoping systematic review, level III.

Outcomes after ultramassive transfusion in the modern era: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era. METHODS: An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality. RESULTS: The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%). CONCLUSION: Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication. LEVEL OF EVIDENCE: Prognostic, level III.

ROTEM in the setting of liver transplant surgery reduces frozen plasma transfusion.

BACKGROUND: INR is traditionally used as a marker of clinical coagulopathy, but is suboptimal in liver disease patients due to rebalanced hemostasis and its ineffectiveness to predict bleeding. Rotational thromboelastometry (ROTEM) testing evaluates whole blood hemostasis, which may provide more accurate assessments with the EXTEM CT parameter than INR. Thus, in end-stage liver disease (ESLD) patients, we hypothesized that elevated INRs are associated with normal EXTEM CT values. METHODS: A retrospective study assessing adult (>18) patients with ESLD and elevated INRs undergoing liver transplantation, was performed to assess correlations between INR and EXTEM CT. This included patients post-ROTEM implementation where all had pre-operative ROTEM testing; and patients up to one year pre-ROTEM implementation to compare transfusion utilization. Data abstracted also included patient demographics, coagulation testing results, liver disease etiology, and MELD score. RESULTS: The study included 138 patients in the post-ROTEM group and 59 patients in the pre-ROTEM group. Normal EXTEM CT was observed in 95.3 % and 93 % of patients with INR of 1.3-1.8 and up to 3 respectively. There was no correlation between INR of 1.3-1.8 and EXTEM CT (⍴ = 0.239), and only moderate correlation was observed with higher INRs (⍴ = 0.617 with INRs >1.8). ROTEM-guided transfusion in liver transplant surgeries was associated with reduced plasma transfusion (OR 0.27, 95 % CI 0.12-0.58, p = 0.001) after adjusting for red cell utilization and coagulation testing. CONCLUSION: Our study suggests ROTEM may be advantageous for evaluating coagulopathy in patients with liver disease and ROTEM-guided transfusion reduces plasma transfusion.

London 2017: Lessons learned in transfusion emergency planning.

BACKGROUND AND OBJECTIVES: Hospitals prepare for emergencies, but the impact on transfusion staff is rarely discussed. We describe the transfusion response to four major incidents (MIs) during a 6-month period. Three events were due to terrorist attacks, and the fourth was the Grenfell Tower fire. The aim of this paper was to share the practical lessons identified. METHODS: This was a retrospective review of four MIs in 2017 using patient administration systems, MI documentation and post-incident debriefs. Blood issue, usage and adverse events during the four activation periods were identified using the Laboratory Information Management System (TelePath). RESULTS: Thirty-four patients were admitted (18 P1, 4 P2, 11 P3 and 1 dead). Forty-five blood samples were received: 24 related to nine MI P1 patients. Four P1s received blood components, three with trauma and one with burns, and 35 components were issued. Total components used were six red blood cells (RBC), six fresh frozen plasma (FFP) and two cryoprecipitate pools. Early lessons identified included sample labelling errors (4/24). Errors resolved following the deployment of transfusion staff within the emergency department. Components were over-ordered, leading to time-expiry wastage of platelets. Careful staff management ensured continuity of transfusion services beyond the immediate response period. Debriefing sessions provided staff with support and enabled lessons to be shared. CONCLUSIONS: Transfusion teams were involved in repeated incidents. The demand for blood was minimal. Workload was related to sample handling rather than component issue. A shared situational awareness would improve stock management. A laboratory debriefing system offered valuable feedback for service improvement, staff training and support.

Transfusion support in COVID-19 patients: Impact on hospital blood component supply during the outbreak.

BACKGROUND: During the COVID-19 outbreak, most hospitals deferred elective surgical procedures to allow space for the overwhelming number of COVID-19 patient admissions, expecting a decrease in routine blood component requirements. However, because transfusion support needs of COVID-19 patients are not well known, its impact on hospital blood supply is uncertain. The objective of this study was to assess the effect of the COVID-19 pandemic on transfusion demand. STUDY DESIGN AND METHODS: Transfusion records during the peak of the COVID-19 pandemic (March 1-April 30, 2020) were reviewed in our center to assess changes in blood requirements. RESULTS: During this period 636 patients received a total of 2934 blood components, which reflects a 17.6% reduction in transfusion requirements with regard to the same period of 2019, and blood donations in Madrid dropped by 45%. The surgical blood demand decreased significantly during the outbreak (50.2%). Blood usage in the hematology and oncology departments remained unchanged, while the day ward demand halved, and intensive care unit transfusion needs increased by 116%. A total of 6.2% of all COVID inpatients required transfusion support. COVID-19 inpatients consumed 19% of all blood components, which counterbalanced the savings owed to the reduction in elective procedures. CONCLUSION: Although only a minority of COVID-19 inpatients required transfusion, the expected reduction in transfusion needs caused by the lack of elective surgical procedures is partially offset by the large number of admitted patients during the peak of the pandemic. This fact must be taken into account when planning hospital blood supply.

Low titer group O whole blood resuscitation: Military experience from the point of injury.

INTRODUCTION: In the far forward combat environment, the use of whole blood is recommended for the treatment of hemorrhagic shock after injury. In 2016, US military special operations teams began receiving low titer group O whole blood (LTOWB) for use at the point of injury (POI). This is a case series of the initial 15 patients who received LTOWB on the battlefield. METHODS: Patients were identified in the Department of Defense Trauma Registry, and charts were abstracted for age, sex, nationality, mechanism of injury, injuries and physiologic criteria that triggered the transfusion, treatments at the POI, blood products received at the POI and the damage-control procedures done by the first surgical team, next level of care, initial interventions by the second surgical team, Injury Severity Score, and 30-day survival. Descriptive statistics were used to characterize the clinical data when appropriate. RESULTS: Of the 15 casualties, the mean age was 28, 50% were US military, and 63% were gunshot wounds. Thirteen patients survived to discharge, one died of wounds after arrival at the initial resuscitative surgical care, and two died prehospital. The mean Injury Severity Score was 21.31 (SD, 18.93). Eleven (68%) of the causalities received additional blood products during evacuation/role 2 and/or role 3. Vital signs were available for 10 patients from the prehospital setting and 9 patients upon arrival at the first surgical capable facility. The mean systolic blood pressure was 80.5 prehospital and 117 mm Hg (p = 0.0002) at the first surgical facility. The mean heart rate was 105 beats per minute prehospital and 87.4 beats per minute (p = 0.075) at the first surgical facility. The mean hospital stay was 24 days. CONCLUSION: The use of cold-stored LTOWB at POI is feasible during combat operations. Further data are needed to validate and inform best practice for POI transfusion. LEVEL OF EVIDENCE: Therapeutic study, level V.

Liquid plasma reduces waste and health care expenses compared with thawed plasma at a Level I trauma center.

BACKGROUND: Balanced resuscitation strategies have led to increased utilization of plasma. Fresh frozen plasma that is thawed and never used is a large source of blood component wastage. Thawed plasma (TP) and can only be stored for 5 days. Liquid plasma (LP) has never been frozen and can be stored for 26 days. Due to longer storage duration, we hypothesized that using LP would result in decreased waste and cost savings compared with TP. METHODS: We performed a retrospective review of all trauma patients at our Level I trauma center in the years 2015 to 2016. We compared 2015 when only TP was used to 2016 when both TP and LP were used. All plasma units ordered for trauma patients were tracked until the time of transfusion or wastage. Wastage rates were compared between years and plasma type. RESULTS: There were 5,789 trauma patients admitted to our institution from 2015 to 2016. There were 4,107 plasma units ordered with 487 (11.9%) units wasted. During 2015, 2,021 total units of plasma were ordered with 273 (13.5%) units wasted which was a significantly higher rate than 2016 when 2,086 total units of plasma were ordered and 214 (10.3%) units were wasted (p = 0.0013). During 2016, 1,739 units of TP were ordered and 204 (11.7%) units were wasted which was significantly higher than LP wastage, 347 units ordered and 10 (2.9%) units wasted (p < 0.001). Of the 477 wasted TP units, 76.9% were ordered no more than two times before being wasted and 95.8% were ordered no more than three times before being wasted. Of the 10 LP units wasted, 40% were ordered no more than two times before being wasted, and 50% were ordered no more than three times before being wasted. If TP was wasted at the same rate as LP, 368 fewer units of plasma would have been wasted representing US $39,376 (US $107/unit) of wasted health care expenses. CONCLUSION: At a Level I trauma center, the addition of LP to the blood bank for trauma resuscitations significantly reduced plasma wastage rates and health care expenses. LEVEL OF EVIDENCE: Level III, Economic/Decision.

Group A emergency-release plasma in trauma patients requiring massive transfusion.

BACKGROUND: Both groups A and AB plasma have been approved for emergency-release transfusion in acutely bleeding trauma patients before blood grouping being performed. The safety profile associated with this practice has not been well characterized, particularly in patients requiring massive transfusion. METHODS: This secondary analysis of the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios trial examined whether exposure to group A emergency-release plasma (ERP) was noninferior to group AB ERP. We also examined patients whose blood groups were compatible with group A ERP versus patients whose blood groups were incompatible with group A ERP. Outcomes included 30-day mortality and complication rates including systemic inflammatory response syndrome, infection, renal injury, pulmonary dysfunction, and thromboembolism. RESULTS: Of the 680 patients predicted to receive a massive transfusion, 584 (85.9%) received at least 1 U of ERP. Of the 584 patients analyzed, 462 (79.1%) received group AB and 122 (20.9%) received group A ERP. Using a hazard ratio (HR) of 1.35 as the noninferiority margin, transfusion with group A versus group AB ERP was not associated with increased thromboembolic rates (HR, 0.52; 95% confidence interval [CI], 0.31-0.90). Mortality (HR, 1.15; 95% CI, 0.91-1.45) and nonfatal complication rates (HR, 1.24; 95% CI, 0.87-1.77) were inconclusive. In the subgroup analysis, transfusion with incompatible ERP (group B or AB patients receiving group A ERP) was not associated with increased nonfatal complications (HR, 1.02; 95% CI, 0.80-1.30). There were no reported hemolytic transfusion reactions. CONCLUSION: The use of ERP is common in patients requiring massive transfusion and facilitates the rapid balanced resuscitation of patients who have sustained blood loss. Group A ERP is an acceptable option for patients requiring massive transfusion, especially if group AB ERP is not readily available. LEVEL OF EVIDENCE: Therapeutic/Care Management, level IV; Prognostic, level III.

Is tranexamic acid effective on hidden blood loss in patients during total knee arthroplasty?

OBJECTIVES: This study aims to investigate if tranexamic acid (TXA) reduces both visible and hidden blood loss in patients undergoing total knee arthroplasty (TKA). PATIENTS AND METHODS: A total of 128 female patients (mean age 68.9±5.8 years; range, 55 to 80 years) who underwent TKA and were admitted between January 2010 and January 2020 were included in this retrospective study. Only patients who had primary unilateral knee arthroplasty with a cemented posterior cruciate ligament substituting implant were included. Patients were divided into two groups according to TXA administration in the perioperative period. Group 1 consisted of patients who did not receive TXA (n=69), while Group 2 consisted of patients who received TXA (n=59). The effect of TXA on visible and hidden blood loss, amount of erythrocyte suspension transfusions, postoperative early wound complications, and the relationship between the volume of hidden blood loss and drainage volume were detected. RESULTS: There was no statistically significant difference between the groups in terms of age, body mass index, operation side, preoperative hematocrit (HCT) values, and total blood volume. Postoperative HCT values were statistically higher in Group 2. Fifty-four units of erythrocyte suspension transfusion were required in Group 1, while six units were required in Group 2 (p<0.001). Early wound complication was determined in 10 patients in Group 1 and only in one patient in Group 2 (p=0.011). Intraoperative blood loss, postoperative drainage volume, hidden blood loss, and total blood loss values were significantly lower in Group 2 (p=0.001). In all patients, there was a significant positive correlation between the postoperative drainage volume and the hidden blood loss volume (r=0.532, p=0.001). CONCLUSION: The use of TXA in patients undergoing TKA reduces postoperative bleeding (visible and hidden blood loss), blood transfusion needs, and early wound complications. In addition, drainage volume in postoperative 24 hours can be used to estimate the amount of hidden blood loss in early postoperative period.

Immunodeficient mice are better for modeling the transfusion of human blood components than wild-type mice.

Animal models are vital to the study of transfusion and development of new blood products. Post-transfusion recovery of human blood components can be studied in mice, however, there is a need to identify strains that can best tolerate xenogeneic transfusions, as well as to optimize such protocols. Specifically, the importance of using immunodeficient mice, such as NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice, to study human transfusion has been questioned. In this study, strains of wild-type and NSG mice were compared as hosts for human transfusions with outcomes quantified by flow cytometric analyses of CD235a+ erythrocytes, CD45+ leukocytes, and CD41+CD42b+ platelets. Complete blood counts were evaluated as well as serum cytokines by multiplexing methods. Circulating human blood cells were maintained better in NSG than in wild-type mice. Lethargy and hemoglobinuria were observed in the first hours in wild-type mice along with increased pro-inflammatory cytokines/chemokines such as monocyte chemoattractant protein-1, tumor necrosis factor α, keratinocyte-derived chemokine (KC or CXCL1), and interleukin-6, whereas NSG mice were less severely affected. Whole blood transfusion resulted in rapid sequestration and then release of human cells back into the circulation within several hours. This rebound effect diminished when only erythrocytes were transfused. Nonetheless, human erythrocytes were found in excess of mouse erythrocytes in the liver and lungs and had a shorter half-life in circulation. Variables affecting the outcomes of transfused erythrocytes were cell dose and mouse weight; recipient sex did not affect outcomes. The sensitivity and utility of this xenogeneic model were shown by measuring the effects of erythrocyte damage due to exposure to the oxidizer diamide on post-transfusion recovery. Overall, immunodeficient mice are superior models for xenotransfusion as they maintain improved post-transfusion recovery with negligible immune-associated side effects.

Dynamic impact of transfusion ratios on outcomes in severely injured patients: Targeted machine learning analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios randomized clinical trial.

BACKGROUND: Massive transfusion protocols to treat postinjury hemorrhage are based on predefined blood product transfusion ratios followed by goal-directed transfusion based on patient's clinical evolution. However, it remains unclear how these transfusion ratios impact patient outcomes over time from injury. METHODS: The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) is a phase 3, randomized controlled trial, across 12 Level I trauma centers in North America. From 2012 to 2013, 680 severely injured patients required massive transfusion. We used semiparametric machine learning techniques and causal inference methods to augment the intent-to-treat analysis of PROPPR, estimating the dynamic relationship between transfusion ratios and outcomes: mortality and hemostasis at different timepoints during the first 24 hours after admission. RESULTS: In the intention-to-treat analysis, the 1:1:1 group tended to have decreased mortality, but with no statistical significance. For patients in whom hemostasis took longer than 2 hours, the 1:1:1 ratio was associated with a higher probability of hemostasis, statistically significant from the 4 hour on. In the per-protocol, actual-transfusion-ratios-received analysis, during four successive time intervals, no significant association was found between the actual ratios and mortality. When comparing patient groups who received both high plasma/PRBC and high platelet/PRBC ratios to the group of low ratios in both, the relative risk of achieving hemostasis was 2.49 (95% confidence interval, 1.19-5.22) during the third hour after admission, suggesting a significant beneficial impact of higher transfusion ratios of plasma and platelets on hemostasis. CONCLUSION: Our results suggest that the impact of transfusion ratios on hemostasis is dynamic. Overall, the transfusion ratios had no significant impact on mortality over time. However, receiving higher ratios of platelets and plasma relative to red blood cells hastens hemostasis in subjects who have yet to achieve hemostasis within 3 hours after hospital admission. LEVEL OF EVIDENCE: Therapeutic IV.

Characterization of unexpected survivors following a prehospital plasma randomized trial.

BACKGROUND: Prehospital plasma improves survival for severely injured trauma patients transported by air ambulance. We sought to characterize the unexpected survivors, patients who survived despite having high predicted mortality after traumatic injury. METHODS: The Prehospital Air Medical Plasma trial randomized severely injured patients (n = 501) to receive either standard care (crystalloid) or two units of prehospital plasma followed by standard care fluid resuscitation. We built a generalized linear model to estimate patient mortality. Area under the receiver operating characteristic curve was used to evaluate model performance. We defined unexpected survivors as patients who had a predicted mortality greater than 50% and survived to 30 days. We characterized patient demographics, clinical features, and outcomes of the unexpected survivors. Observed to expected (O/E) ratios and Z-statistics were calculated using model-estimated mortality for each cohort. RESULTS: Our model predicted mortality better than Injury Severity Score or Revised Trauma Score parameters and identified 36 unexpected survivors. Compared with expected survivors, unexpected survivors were younger (33 years [24, 52 years] vs. 47 years [32, 59 years], p = 0.013), were more severely injured (Injury Severity Score 34 [22, 50] vs. 18 [10, 27], p < 0.001), had worse organ dysfunction and hospital resource outcomes (multiple organ failure, intensive care unit, hospital length of stay, and ventilator days), and were more likely to receive prehospital plasma (67 vs. 46%, p = 0.031). Nonsurvivors with high predicted mortality were more likely to receive standard care resuscitation (p < 0.001). Unexpected survivors who received prehospital plasma had a lower observed to expected mortality than those that received standard care resuscitation (O/E 0.56 [0.33-0.84] vs. 1.0 [0.73-1.32]). The number of prehospital plasma survivors (24) exceeded the number of predicted survivors (n = 10) estimated by our model (p < 0.001). CONCLUSION: Prehospital plasma is associated with an increase in the number of unexpected survivors following severe traumatic injury. Prehospital interventions may improve the probability of survival for injured patients with high predicted mortality based on early injury characteristics, vital signs, and resuscitation measures. LEVEL OF EVIDENCE: Therapeutic Level III.

Prehospital plasma in injured patients is associated with survival principally in blunt injury: Results from two randomized prehospital plasma trials.

INTRODUCTION: Recent evidence demonstrated that prehospital plasma in patients at risk of hemorrhagic shock was safe for ground transport and resulted in a 28-day survival benefit for air medical transport patients. Whether any beneficial effect of prehospital plasma varies across injury mechanism remains unknown. METHODS: We performed a secondary analysis using a harmonized data set derived from two recent prehospital plasma randomized trials. Identical inclusion/exclusion criteria and primary/secondary outcomes were used for the trials. Prehospital time, arrival shock parameters, and 24-hour transfusion requirements were compared across plasma and control groups stratified by mechanism of injury. Stratified survival analysis and Cox hazard regression were performed to determine the independent survival benefits of plasma across blunt and penetrating injury. RESULTS: Blunt patients had higher injury severity, were older, and had a lower Glasgow Coma Scale. Arrival indices of shock and coagulation parameters were similar across blunt and penetrating injury. The percentage of patients with a prehospital time less than 20 minutes was significantly higher for penetrating patients relative to blunt injured patients (28.0% vs. 11.6%, p < 0.01). Stratified Kaplan-Meier curves demonstrated a significant separation for blunt injured patients (n = 465, p = 0.01) with no separation demonstrated for penetrating injured patients (n = 161, p = 0.60) Stratified Cox hazard regression verified, after controlling for all important confounders, that prehospital plasma was associated with a 32% lower independent hazard for 28-day mortality in blunt injured patients (hazard ratio, 0.68; 95% confidence interval, 0.47-0.96; p = 0.03) with no independent survival benefit found in penetrating patients (hazard ratio, 1.16; 95% confidence interval, 0.4-3.1; p = 0.78). CONCLUSION: A survival benefit associated with prehospital plasma at 24 hours and 28 days exists primarily in blunt injured patients with no benefit shown in penetrating trauma patients. No detrimental effects attributable to plasma are demonstrated in penetrating injury. These results have important relevance to military and civilian trauma systems. LEVEL OF EVIDENCE: Therapeutic, I.

A novel protocol to maintain continuous access to thawed plasma at a rural trauma center.

BACKGROUND: Early administration of plasma improves mortality in massively transfused patients, but the thawing process causes delay. Small rural centers have been reluctant to maintain thawed plasma due to waste concerns. Our 254-bed rural Level II trauma center initiated a protocol allowing continuous access to thawed plasma, and we hypothesized its implementation would not increase waste or cost. METHODS: Two units of thawed plasma are continuously maintained in the trauma bay blood refrigerator. After 3 days, these units are replaced with freshly thawed plasma and returned to the blood bank for utilization prior to their 5-day expiration date. The blood bank monitors and rotates the plasma. Only trauma surgeons can use the plasma stored in the trauma bay. Wasted units and cost were measured over a 12-month period and compared with the previous 2 years. RESULTS: The blood bank thawed 1127 units of plasma during the study period assigning 274 to the trauma bay. When compared with previous years, we found a significant increase in waste (p < 0.001) and cost (p = 0.020) after implementing our protocol. It cost approximately US $125/month extra to maintain continuous access to thawed plasma during the study period. DISCUSSION: A protocol to maintain thawed plasma in the trauma bay at a rural Level II trauma center resulted in a miniscule increase in waste and cost when considering the scope of maintaining a trauma center. We think this cost is also minimal when compared with the value of having immediate access to thawed plasma. Constant availability of thawed plasma can be offered at smaller rural centers without a meaningful impact on cost. LEVEL OF EVIDENCE: Economic and Value-based Evaluations, Level III.