Massive Transfusion Protocol Adherence: Relationship to Trauma Patient Outcomes.

BACKGROUND: Ongoing evaluation of massive transfusion protocol adherence is critical to ensure better trauma patient outcomes. OBJECTIVE: This quality improvement initiative aimed to determine provider adherence to a recently revised massive transfusion protocol and its relationship to clinical outcomes among trauma patients requiring massive transfusion. METHODS: A retrospective, descriptive, correlational design was used to determine the association between provider adherence to a recently revised massive transfusion protocol and clinical outcomes in trauma patients with hemorrhage treated at a Level I trauma center from November 2018 to October 2020. Patient characteristics, provider massive transfusion protocol adherence, and patient outcomes were assessed. Patient characteristics and massive transfusion protocol adherence associations with 24-hr survival and survival to discharge were determined using bivariate statistical methods. RESULTS: A total of 95 trauma patients with massive transfusion protocol activation were evaluated. Of the 95, 71 (75%) survived the initial 24 hr following massive transfusion protocol activation and 65 (68%) survived to discharge. Based on protocol applicable items, the median massive transfusion protocol overall adherence rate per patient was 75% (IQR = 57.1-85.7) for the 65 survivors and 25% (IQR = 12.5-50.0) for the 21 nonsurvivors to discharge whose death occurred at least 1 hr after massive transfusion protocol activation (p < .001). CONCLUSION: Findings indicate the importance of ongoing evaluations of adherence to massive transfusion protocols in hospital trauma settings to target areas for improvement.

Hospital red blood cell and platelet supply and utilization from March to December of the first year of the COVID-19 pandemic: The BEST collaborative study.

BACKGROUND: At the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19. STUDY DESIGN AND METHODS: Weekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline). RESULTS: RBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p < .001) and 5% fewer RBCs were transfused per week compared to 2019 (477 vs. 501, p < .001). However, during the first COVID-19 peak, RBC and PLT inventories were higher than normal, as reflected by deviation from par, days on hand, and percent outdated. At this time, 16% fewer inpatient beds were occupied, and 43% fewer surgeries were performed compared to 2019 (p < .001). In contrast to 2019 when there was no correlation, there was, in 2020, significant negative correlations between RBC and PLT days on hand and both percentage occupancy of inpatient beds and percentage of surgeries performed. CONCLUSION: During the COVID-19 pandemic in 2020, RBC and PLT inventories remained adequate. During the first wave of cases, significant decreases in patient care activities were associated with excess RBC and PLT supplies and increased product outdating.

Massive Transfusion Protocol Predictive Modeling in the Modern Electronic Medical Record.

Objectives: Integrate a predictive model for massive transfusion protocol (MTP) activation and delivery in the electronic medical record (EMR) using prospectively gathered data; externally validate the model and assess the accuracy and precision of the model over time. Background: The Emory model for predicting MTP using only four input variables was chosen to be integrated into our hospital's EMR to provide a real time clinical decision support tool. The continuous variable output allows for periodic re-calibration of the model to optimize sensitivity and specificity. Methods: Prospectively collected data from level 1 and 2 trauma activations were used to input heart rate, systolic blood pressure, base excess (BE) and mechanism of injury into the EMR-integrated model for predicting MTP activation and delivery. MTP delivery was defined as: 6 units of packed red blood cells/6 hours (MTP1) or 10 units in 24 hours (MTP2). The probability of MTP was reported in the EMR. ROC and PR curves were constructed at 6, 12, and 20 months to assess the adequacy of the model. Results: Data from 1162 patients were included. Areas under ROC for MTP activation, MTP1 and MTP2 delivery at 6, 12, and 20 months were 0.800, 0.821, and 0.831; 0.796, 0.861, and 0.879; and 0.809, 0.875, and 0.905 (all P < 0.001). The areas under the PR curves also improved, reaching values at 20 months of 0.371, 0.339, and 0.355 for MTP activation, MTP1 delivery, and MTP2 delivery. Conclusions: A predictive model for MTP activation and delivery was integrated into our EMR using prospectively collected data to externally validate the model. The model's performance improved over time. The ability to choose the cut-points of the ROC and PR curves due to the continuous variable output of probability of MTP allows one to optimize sensitivity or specificity.

Comparison of the platelet activation status of single-donor platelets obtained with two different cell separator technologies.

BACKGROUND: The microparticle content (MP%) of apheresis platelets-a marker of platelet activation-is influenced by donor factors and by external stressors during collection and storage. This study assessed the impact of apheresis technology and other factors on the activation status (MP%) of single-donor apheresis platelets. STUDY DESIGN AND METHODS: Data from six US hospitals that screened platelets by measuring MP% through dynamic light scattering (ThromboLUX) were retrospectively analyzed. Relative risks (RRs) were derived from univariate and multivariable regression models, with activation rate (MP% ≥15% for plasma-stored platelets; ≥10% for platelet additive solution [PAS]-stored platelets) and MP% as outcomes. Apheresis platform (Trima Accel vs Amicus), storage medium (plasma vs PAS), pathogen reduction, storage time, and testing location were used as predictors. RESULTS: Data were obtained from 7511 platelet units collected using Trima (from 16 suppliers, all stored in plasma, 20.0% were pathogen-reduced) and 2456 collected using Amicus (from four different collection facilities of one supplier, 65.0% plasma-stored, 35.0% PAS-stored, none pathogen-reduced). Overall, 30.0% of Trima platelets were activated compared to 45.6% of Amicus platelets (P < .0001). Multivariable analysis identified apheresis platform as significantly associated with platelet activation, with a lower activation rate for Trima than Amicus (RR: 0.641, 95% confidence interval [CI]: 0.578; 0.711, P < .0001) and a 6.901% (95% CI: 5.926; 7.876, P < .0001) absolute reduction in MP%, when adjusting for the other variables. CONCLUSION: Trima-collected platelets were significantly less likely to be activated than Amicus-collected platelets, irrespective of the storage medium, the use of pathogen reduction, storage time, and testing site.

Effects of repleting organic phosphates in banked erythrocytes on plasma metabolites and vasoactive mediators after red cell exchange transfusion in sickle cell disease.

BACKGROUND: Red blood cell (RBC) exchange (RCE) transfusion therapy is indicated for certain patients with sickle cell disease (SCD). Although beneficial, this therapy is costly and inconvenient to patients, who may require it monthly or more often. Identification of blood and plasma biomarkers that could improve or help individualise RCE therapy is of interest. Here we examined relevant blood and plasma metabolites and biomarkers of vasoactivity and RBC fragility in a pilot study of SCD patients undergoing RCE using either standard RBC units or RBC units treated with a US Food and Drug Administration (FDA)-approved additive solution containing phosphate, inosine, pyruvate, and adenine ("PIPA"). MATERIALS AND METHODS: In this prospective, single-blind, cross-over pilot clinical trial, patients were randomised to receive either standard RBC exchange or PIPA-treated RBC exchange transfusion with each RCE session over a 6-month treatment period. Pre- and post-transfusion blood samples were obtained and analysed for RBC O2 affinity, ATP, purine metabolites, RBC microparticles, and cell free haemoglobin. RESULTS: Red blood cell O2 affinity was maintained after PIPA-RCE in contrast to standard RCE, after which P50 fell (net O2 affinity rose). Plasma ATP did not change significantly after RCE using either of the RBC unit types. Exchange transfusion with PIPA-treated RBC units led to modest increases in plasma inosine and hypoxanthine. Plasma cell free haemoglobin fell after either standard or PIPA-treated RBC exchange transfusion (novel findings), and to a similar extent. RBC-derived microparticles in the plasma fell significantly and similarly after both standard and PIPA-treated RCE transfusion. DISCUSSION: In summary, treatment of RBCs with PIPA prior to RCE elicited favourable or neutral changes in key metabolic and vascular biomarkers. Further study of its efficacy and safety is recommended and could ultimately serve to improve outcomes in chronically transfused SCD patients.

Rejuvenation solution as an adjunct cold storage solution maintains physiological haemoglobin oxygen affinity during early-storage period of red blood cells.

BACKGROUND: Red blood cell (RBC) units accumulate morphologic and metabolic lesions during storage before transfusion. Pyruvate-inosine-phosphate-adenine (PIPA) solutions (Rejuvesol, Biomet, Warsaw, IN) can be incubated with RBC units to mitigate storage lesions. This study proposes a PIPA treatment process, termed cold 'rejuvenation', using Rejuvesol as an adjunct additive solution, to prevent biomechanical storage lesions while avoiding the 1 h PIPA incubation required with standard PIPA treatment. We compared the efficacy of cold to standard 'rejuvenation' in improving metabolic lesions that occur during cold storage of RBCs, without altering function. METHODS: Twelve leucoreduced, A-positive RBC units were obtained. Each unit was aliquoted into either control (standard storage), washed (W), standard rejuvenation (SR) or cold rejuvenation (CR) groups, the latter two requiring washing. A volume-adjusted dose of Rejuvesol was instilled into the CR group upon receipt (Day 3). After 15 days of storage, p50, RBC deformability, in-bag haemolysis and mechanical fragility were analysed. 'Any treatment' is defined as W, SR and CR, with comparisons in reference to control. RESULTS: Higher p50s were seen in rejuvenated groups (>30 mmHg vs. <19 mmHg; P < 0·0001). Any treatment significantly increased elongation index (P = 0·034) but did not significantly increase in-bag haemolysis (P = 0·062). Mechanical fragility was not significantly different between groups (P = 0·055) at baseline, but the control (CTL) group was more fragile after 2 h in a cardiac bypass simulation than any treatment (P < 0·0001). CONCLUSIONS: This study demonstrates that rejuvenation (standard or cold) prevents the leftward p50 shift of storage lesions without detrimental effect on RBC deformity, in-bag haemolysis or mechanical fragility.

Interval decline in hemoglobin A is associated with annual clinical event rate in sickle cell anemia patients receiving maintenance apheresis RBC exchange.

BACKGROUND: Apheresis red blood cell (RBC) exchange (RCE) is a standard intervention for patients with sickle cell anemia (SCA) who have had previous thromboembolic stroke or intractable chronic pain. Replacing sickling cells with those containing hemoglobin A (HbA) minimizes microvascular pathophysiology that produces clinical crises. Limited data exist regarding the interval changes in HbA between transfusions. We sought to describe the HbA decrement between RCE procedures and its relationship to clinical status. STUDY DESIGN AND METHODS: SCA patients (all hemoglobin SS disease) treated with maintenance RCE (n = 21) over a 15-month period at two neighboring institutions were retrospectively reviewed. Time-normalized daily HbA decrement was calculated to reflect loss of transfused RBCs, and annual events of either emergency department or hospital admissions for SCA complications were noted. Associations between HbA decrement and laboratory measures were calculated using mixed linear regression models and unpaired t test was used to compare HbA decrement between high and low event rate groups. RESULTS: A total of 31 events were recorded, and mean HbA decrement per day was 0.77 ± 0.16%. The mean interval between RCEs was 36 ± 12 days. Patients with more annual events exhibited a significantly greater daily HbA decrement (p = 0.007). No significant association between RBC unit age and HbA decrement or annual event rate was observed. CONCLUSIONS: Patients exhibiting greater daily HbA decrement were more likely to have multiple emergency department visits or admissions for sickling crises. Modulating HbA decrement may merit study as an intermediate metric for interventions to improve outcomes in hemoglobin SS disease.

Massive transfusion in the pediatric population: A systematic review and summary of best-evidence practice strategies.

BACKGROUND: Pediatric patients require massive transfusion (MT) in a variety of settings. Multiple studies of adult MT support balanced ratio transfusion to improve outcomes; however, it is unclear if these findings can be extrapolated to pediatric populations. The use of balanced transfusion ratios, MT protocols, hemostatic adjuncts, and even the definition of a MT in children are all open questions. This review presents details of care from current practices in pediatric MT and summarizes practice strategies while providing insight from our single-center experience. METHODS: PubMed, EMBASE, and Web of Science were searched using MeSH index and free-text terms for articles from 1946 to 2017. Articles were independently reviewed by two reviewers. Studies were assessed for definition of MT, factors predicting MT, MT complications, blood product ratios, hemostatic adjuncts, protocol logistics, and clinical outcomes. RESULTS: A heterogeneous composite of 29 articles was included in the analysis. Of these, 45% reported a formal transfusion protocol or adopted one during the study. Seven unique definitions of pediatric MT were reported; the most common was >1 total blood volume within 24 hours. A total of 18,369 patients were assessed, and 1,163 received MT (6.3%). Overall mortality for patients requiring MT in studies reporting mortality was high (range 14.7% to 51.2%). We identified 14 patients receiving MT at our center with an age range of 8 months to 18 years and average transfusion of 38.1 mL/kg red blood cells (range: 22.1 mL/kg to 156.7 mL/kg). CONCLUSIONS: Current practices of pediatric MT demonstrate a variety of site-specific interventions with a persistently high mortality rate. A national focus on improving techniques of MT in children has the potential to save the lives of these children. LEVEL OF EVIDENCE: Systematic review, levels IV and V.

Estimation of Achievable Oxygen Consumption Following Transfusion With Rejuvenated Red Blood Cells.

Erythrocyte storage induces a nonphysiological increase in hemoglobin-oxygen affinity (quantified by low p50, the oxygen tension at 50% hemoglobin saturation), which can be restored through biochemical rejuvenation. The objective was to mathematically model the impact of transfusing up to 3 standard allogeneic units or rejuvenated units on oxygen delivery (DO2) and oxygen consumption (VO2). Oxygen dissociation curves were generated from additive solution-1 red blood cell (RBC) leukoreduced units (n = 7) before and after rejuvenation following manufacturer's instructions. Two of these units were used to prepare standard or rejuvenated donor RBC and added to samples of fresh whole blood. These admixtures were used to construct an in vitro transfusion model of postoperative anemia and determine a linear equation for calculating the sample p50, which was subsequently used to calculate DO2 and VO2 after simulated transfusions. Whole blood-packed red blood cell unit admixture p50s could be predicted from a linear model including the p50 of its components, the mass fraction of the transfused component, and interaction terms (R2 = .99, P < 0.001). Transfusion with standard units slightly, but significantly, increased projected DO2 compared with rejuvenated units (P = 0.03), but rejuvenated units markedly increased projected VO2 (P = 0.03). Standard units did not significantly change VO2 relative to pre-transfusion levels (P > 0.1). Using high-p50, rejuvenated RBC in simulated transfusions greatly improved projected VO2, indicating the potential for increased end-organ oxygen availability compared with standard transfusion. Patient capacity to increase cardiac output after cardiac surgery may be limited. Transfusing high-p50 RBC in this setting may improve the perioperative care of these patients.

Anti-Jka that are detected by solid-phase red blood cell adherence but missed by gel testing can cause hemolytic transfusion reactions.

BACKGROUND: Kidd blood group antibodies are notorious for transient detection and hemolytic transfusion reactions. This report compares the rate of detection of anti-Jka when using gel column agglutination versus solid-phase red blood cell adherence (SPRCA) testing and documents the occurrence of hemolytic transfusion reactions in 17 recently transfused patients who developed anti-Jka that were detectable by SPRCA but were undetectable by gel. STUDY DESIGN AND METHODS: Before April 20, 2011, the laboratory used gel column agglutination as the primary method for antibody screening and identification. From April 20, 2011, to August 12, 2013, SPRCA was adopted as the primary method for antibody screen with gel remaining the primary method for identification. SPRCA identification was also performed if sufficient sample was available. Medical records were reviewed for evidence of hemolytic reaction in patients whose anti-Jka was negative or inconclusive by gel, but clearly identifiable by SPRCA at the time the anti-Jka was first identified. RESULTS: A total of 105 patients were discovered with anti-Jka from 88,478 SPRCA screens performed. In 32 patients, anti-Jka was initially discovered by SPRCA testing and concurrent gel testing was completely negative (n = 26) or inconclusive (n = 6). Seventeen of the 32 patients were recently transfused and of these six met criteria for delayed hemolytic transfusion reaction (DHTR), three had possible DHTRs, and eight had delayed serologic reactions; 13 of the transfused patients received Jk(a-) RBCs to avoid potential hemolysis. CONCLUSION: SPRCA testing significantly increased the discovery of clinically significant anti-Jka and facilitated the earlier use of Jk(a-) RBCs to avoid hemolytic transfusion reactions.

Inventory management strategies that reduce the age of red blood cell components at the time of transfusion.

BACKGROUND: There has been interest concerning patient outcomes when older red blood cell (RBC) components are utilized. Inventory management is key to maintaining a stock of fresher RBCs for general transfusion needs. We have altered our practice for RBC management to reduce RBC age at the time of transfusion. STUDY DESIGN AND METHODS: Retrospective review of RBC age at time of transfusion at a tertiary care hospital with active trauma service was performed. The baseline nonirradiated RBC inventory was decreased from 12 to 15 days of stock to 7 to 10 days of stock, with request made to the blood supplier for fresher RBCs, specified at 75% of RBCs less than 14 days old. The age of RBCs at time of receipt and at time of transfusion was tracked on a monthly basis for the next 12 months. RESULTS: The mean age of RBCs at transfusion was decreased by 9 days on average for the year. Significant decreases in the mean age of RBCs at transfusion were seen in the second half of the year, with 4 of 6 months seeing a mean age of less than 20 days. There were no documented incidences of hospital blood shortages after the reduction in inventory; no surgery was canceled or delayed because of inventory. CONCLUSION: Inventory age depends on active management, combined with vendor cooperation to receive fresher components. Reducing the age of RBC components transfused is possible without experiencing blood component shortages. Longer periods of observation may allow for further adjustment of stocking levels on a seasonal basis.

Non-specific red cell reactivity in an obstetric population.

OBJECTIVE: To examine non-specific red cell reactivity (NSR) on antibody (Ab) screening of obstetric inpatients. METHODS: Observational study of 5438 obstetric inpatients (2009-2013). Ab-positive patients were identified and their records reviewed for NSR, other antibodies, transfusion reactions or hemolytic disease of the fetus/newborn (HDFN). Evaluation of NSR frequency by test era assessed the impact of an institutional change to solid-phase screening in 2011. RESULTS: Of obstetric inpatients, 5.3% had at least one positive Ab screen; 1.6% had NSR. Of NSR-positive patients, 16.7% had identifiable Abs that pre-dated NSR; 25% had concurrent Abs and 8.5% had subsequent Ab identification. In 49.1%, NSR resolved during follow-up. The frequency of NSR was higher after the change to solid-phase Ab screening, but specific Ab frequency was similar in both testing periods. No transfusion reactions or cases of HDFN were noted in this cohort. CONCLUSIONS: NSR is found in 1-2% of obstetrical inpatients at our institution, and has more than doubled since the initiation of solid-phase screening. Although likely clinically insignificant by itself, NSR is commonly found in relation to other red cell Abs and may precede their development.

The treatment of nephrogenic systemic fibrosis with therapeutic plasma exchange.

BACKGROUND: Nephrogenic systemic fibrosis (NSF), also known as nephrogenic sclerosing dermopathy (NSD), is a rare progressive fibrosing disease associated with gadolinium based dyes in patients with renal disease. The exact pathophysiology is not well understood. Accepted treatments include corticosteroids, immune modulators, PUVA, rituximab and extracorporeal photopheresis (ECP). Apheresis is utilized when symptoms continue to progress. However, the paucity of centers offering ECP can be inhibitory to care. Small case reports have been published illustrating moderate treatment success with therapeutic plasma exchange (TPE). METHODS: Chart review found two patients; both were African-American women with systemic lupus erythematosus (SLE), status post renal transplant, who had biopsy documented NSF. The patients were still symptomatic, despite maximal medical management, so they underwent TPE series for symptom management. Medical therapy with immune modulators was continued in conjunction to TPE. Response to treatment was evaluated using subjective reporting to the primary care team. RESULTS: The patients reported significant improvements in subjective pain levels after TPE. Patient 1 reported decreased skin and contracture pain after the 3rd treatment, with similar results for a second series 6 months later. Patient 2 reported drastic improvement in pain symptoms and rarely required pain medication during hospital course. No adverse reactions occurred during treatment. CONCLUSIONS: TPE is a therapy option for patients with NSF without access to ECP. TPE was well-tolerated, easily assessable, and effective; however the etiology of the improvement following TPE is unknown. Larger studies will help further determine the efficacy of TPE for NSF.

Seasonal association of thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a clinical diagnosis, characterized by microangiopathic hemolytic anemia and thrombocytopenia without another likely explanation. Some initiators of the disease are well represented in the literature, such as certain drugs, malignancies, and viral illness; however, there are less objective factors still being investigated, with references to hormonal, stress, and seasonal variations considered anecdotally. A better insight of these factors would aid in understanding the pathophysiology of the disease. STUDY DESIGN AND METHODS: We performed a retrospective review of all idiopathic TTP cases treated with therapeutic plasma exchange at our institution from 1999 to 2008 to determine whether there was seasonal variation in TTP presentation. Seasons were defined as follows: winter = December to February; spring = March to May; summer = June to August; and fall = September to November. With the use of Poisson regression models, the incidence between seasons was compared. RESULTS: During this study period, a total of 97 cases were recorded. Summer had the highest occurrence of TTP (35%). This was significant compared to the fall (p = 0.012) and the winter (p = 0.019). There were more cases in the summer compared to the spring, but this was not significant. CONCLUSION: In our population, there was a significant difference in the number of TTP cases presenting in summer compared to fall and winter. This supports a possible environmental, infectious, or physiologic influence associated with the summer.

Rapid increases in parasitemia following red cell exchange for malaria.

Exchange transfusion is frequently used as an adjunctive treatment of severe malaria, although the efficacy of exchange transfusion as therapy for severe malaria remains controversial. The major perceived benefit of exchange transfusion is the rapid reduction of parasite load. However, no previous report has shown the dynamic change in parasitemia shortly following an acute load reduction. We report a 20-year-female who developed cerebral malaria and 30% parasitemia after traveling to Africa. In addition to antimalarial treatment, red cell exchange (RCX) was begun emergently with an automated blood-cell separator. Parasitemia dropped from 30 to 15% immediately after the procedure but rapidly increased to 25% after 50 min. The second procedure was performed 12 h after the first procedure. Her neurologic status returned to baseline on Day 2, and she was discharged on Day 6. Rapid increases in parasitemia can be observed after mechanical load reduction following RCX.