This retrospective study evaluated the efficacy and total cost of switching from filgrastim (Neupogen) to its biosimilar, filgrastim-aafi (Nivestym), for allogeneic peripheral blood stem cell collection (PBSCC). Among 127 donors, Nivestym and Neupogen showed comparable mobilization outcomes, achieving similar CD34 + cell counts and one-day collection success rates for ≥ 2.0 × 10⁶ and ≥ 4.0 × 10⁶ CD34 + cells/kg recipient weight. Nivestym offered significant reduction in total cost, with an average of $5171.92 versus $6288.76 (p < 0.0001). These findings support Nivestym as a viable alternative, highlighting the importance of evaluating both clinical outcomes and financial implications for biosimilar adoption.

The use of normothermic machine perfusion (NMP) over static cold storage in liver transplantation has been shown to reduce posttransplant risks of early allograft dysfunction, primary nonfunction, and ischemic cholangiopathy, and its increasing use has played a role in the expanded utilization of marginal livers. While studies have demonstrated improved clinical outcomes using NMP over static cold storage preservation, real-time intraoperative data reflecting the quality and viability of NMP livers is limited. This retrospective, single-center study compared NMP versus static cold storage livers in first-time recipients of liver transplants through the evaluation of synthetic coagulation function as measured by thromboelastography and conventional coagulation testing. Secondarily, transfusion utilization between the 2 cohorts was reviewed. One hundred eighty-six recipients of liver transplants receiving allografts from donors after circulatory death were included in the study, of which 99 (53%) allografts were preserved in static cold storage, and 87 (47%) allografts were placed on the TransMedics Organ Care System. Study findings showed NMP livers supported with the TransMedics Organ Care System were associated with increased synthetic coagulation function and less excess fibrinolysis in the postreperfusion period compared to static cold storage livers, and that these findings were better reflected in real-time with thromboelastography monitoring versus conventional coagulation testing. Following reperfusion, there was a significant decrease in the transfusion of blood products in the NMP group compared with that in the static cold storage group. Overall, we determined that the use of intraoperative thromboelastography can provide real-time data to assess one aspect of reperfusion liver quality and viability.

Background Blood and plasma volume calculations are a daily part of practice for many Transfusion Medicine and Apheresis practitioners. Though many formulas exist, each facility may have their own modifications to consider. ChatGPT (Generative Pre-trained Transformer) provides a new and exciting pathway for those with no programming experience to create personalized programs to meet the demands of daily practice. Additionally, this pathway creates computer programs that provide accurate and reproducible outputs. Herein, we aimed to create a step-by-step process for clinicians to create customized computer programs for use in everyday practice. Methods We created a process of inputs to ChatGPT-40, which generated computer programming code. This code was copied and pasted into Notepad (and saved as a Python file) and Google Colaboratory to verify functionality. We validated the durability of our process by repeating it over a 5-day timeframe and by recruiting volunteers to reproduce our outputs using the suggested process. Results Computer code generated by ChatGPT-40 in response to our common language inputs was accurate and durable over time. The code was fully functional in both Python and Colaboratory. Volunteers reproduced our process and outputs with minimal assistance. Conclusion We analyzed the practical application of ChatGPT-40 and artificial intelligence (AI) to perform daily calculations encountered in Transfusion Medicine. Our results provide a proof of concept that people with no programming experience can create customizable solutions for their own facilities. Our future work will expand to the creation of comprehensive and customizable websites designed for each individual user.

Intravenous immune globulin (IVIG) is a common treatment given after plasma exchange procedures to either prevent secondary hypogammaglobulinemia or as an adjunctive treatment for organ transplant rejection. However, side-effects are relatively common with this medication during and after infusion. This case-report describes our alternative to IVIG infusions post-plasma exchange. We hypothesize that in patients unable to tolerate IVIG, using thawed plasma as a replacement fluid provides a suitable increase in the patients post procedure immunoglobulin G (IgG) levels for patients with secondary hypogammaglobulinemia that are unable to tolerate IVIG infusions.

This manuscript describes a novel approach for treating patients with long-term sequelae from hemoglobin Evans (Hb Evans). After instituting conservative therapies for approximately 2 years, our patient's symptoms continually worsened. Therefore, we performed red blood cell exchange (RBCx) to reduce his Hb Evans percentage and his co-existing elevation of methemoglobin. Our assumptions of clinical benefit were based on our collective experience performing RBCx for patients with sickle cell disease. After the first exchange, pre- and post-laboratory results supported our approach and the patient experienced marked improvement in his clinical signs and symptoms. This report provides preliminary proof of principle for the use of RBCx to treat Hb Evans and other non-Hb S hemoglobinopathies.

BACKGROUND:Cromer antigens are carried on decay accelerating factor (DAF, CD55), for which the crystal structure is available. We investigated two samples with an unidentified antibody to a high prevalence antigen and evaluate the location and characteristics of amino acids associated with antigens on the CD55 by 3D modelling.MATERIALS AND METHODS:Antigen typing and antibody identification were by standard methods. CD55 was sequenced, and Cromer variants were generated using the protein's crystal structure (1OK3, chain A). Antigen-associated residues and intraprotein interactions were investigated in 3D (Naccess, Protein Interactions Calculator).RESULTS:The antibody in the sample from a woman of Kashmiri descent was identified as anti-IFC (anti-CROM7). Her RBCs were negative for high-prevalence Cromer antigens including IFC. CD55 sequencing revealed a silent c.147G>A (p.Leu49=) and c.148G>T (p.Glu50Ter) changes, designated CROM*01N.05. The antibody in the sample from a woman of Greek ancestry was only compatible with IFC- RBCs but her RBCs were positive for known high-prevalence Cromer antigens. CD55 sequencing found she was homozygous for c.173A>G (p.Asp58Gly). The high prevalence antigen was named CRAG (ISBT CROM18 or 021018) and the allele designated CROM*01.-18. By 3D analysis, all known antigen-associated residues, including the new CRAG antigen, were exposed at the protein surface. Interactions between antigen-associated residues within the same CD55 domains were identified.DISCUSSION:Identification of antibodies to high prevalence Cromer antigens can be challenging. The surface exposure of antigen-associated residues likely accounts for their immunogenicity. 3D analysis of CD55 provides insight into previous serologic observations regarding the influence of some Cromer antigens on the expression of others.

Godby, Richard Curtisa; Raju, Dheerajb; Massicano, Felipea; Williams, Lance A.c; Black, Brileya; Dorn, Davidd; Marques, Marisa B.a Author Information

Prekallikrein (PK) deficiency is extremely rare, and manifestations are not well characterized due to a small number of cases reported and the lack of scientific clarity about its role in clot formation in vivo. Here, we report a case of a 64-year-old male, with no known history of abnormal bleeding, who scheduled to undergo deep brain stimulator placement for control of his Parkinson's disease. During pre-procedure testing, activated partial thromboplastin time (PTT) was found to be prolonged at 146 seconds. Mixing studies were suggestive of a coagulation factor deficiency. His PTT characteristically became shorter with prolonged incubation, providing a clue at testing for PK levels, which were found to be severely low. He, subsequently, underwent surgery without any complications. Our case further highlights the clinical pearls for diagnosis and further endorses that these patients can safely undergo surgical procedures without the need for plasma transfusions or factor concentrate usage.

Purpose During a national shortage of calcium gluconate, we switched to calcium chloride for routine supplementation for peripheral blood stem cell (PBSC) collections. Subsequently, we analyzed the postprocedure ionized calcium level, as we aimed for an equivalent result compared to before the shortage. Methods Pharmacy representatives helped us to find an "equivalent" substitute for calcium gluconate at 46.5 mEq in 500 mL normal saline, infused at 100 mL/hour. After instituting a presumably comparable protocol using calcium chloride (40.8 mEq in 250 mL normal saline at a rate of 100 mL/hour), we reviewed ionized calcium results post-PBSC procedures to compare with those obtained with calcium gluconate. Having noticed a difference in the mean values, we adjusted the rate of calcium chloride to reach our desired outcome. Results Twenty-seven procedures were analyzed on 15 unique patients. We used the Spectra OPTIA with a whole blood: anticoagulant ratio of 13:1. Ionized calcium levels post-PBSC collection with the first calcium chloride protocol were significantly higher (P = 0.003) in nine patients treated. Subsequently, we decreased the calcium chloride infusion rate to 75 mL/hour and achieved similar mean levels to calcium gluconate (P = 0.382). Conclusion Changes in replacement fluids for apheresis procedures can be complex, particularly when dealing with electrolytes that could be clinically significant at critically high or low levels. Once we recognized the need to take into account the amount of elemental calcium infused, we achieved the desired postprocedure ionized calcium results. This study can serve as a lesson for future shortages of infusions used during apheresis procedures.

Background: Treatment of multiple myeloma with daratumumab (DARA) is increasing fast. Unfortunately, this antibody also attaches to red blood cells (RBCs) and mimics an autoantibody's panreactivity during pre-transfusion testing, necessitating specialized techniques, (e.g. dithiothreitol (DTT)) for alloantibody detection. Many hospitals use a reference lab for such testing, increasing both cost and turn-around time (TAT). Herein, we compare the cost and TAT, pre and post-implementation of an in-house DTT protocol. Methods: We designed a validation of our in-house DTT protocol from Nov to Dec 2017 with full implementation on January 1, 2018. We retrospectively reviewed all pre-transfusion tests on DARA patients from Feb 2016 to April 2018, pre and post-implementation of in-house DTT testing. Descriptive statistics were used for patient demographics and a Student t-test was used to compare cost and TATS (pre and post-implementation). Results: We identified 49 patients on DARA treatment requiring transfusion. Samples from these patients were sent to the reference lab 104 times and were tested in-house 28 times. The average TAT for the reference lab was 19h25 m compared to our in-house TAT of 5h9m (an average time-savings of 14h16 m). We spent approximately $33,800 ($325 per test) for 104 reference lab samples versus $806.12 (128.79 per test) for in-house testing of 28 samples. Conclusion: We provide an easily implementable DTT protocol for pre-transfusion testing community hospitals and beyond. As more monoclonal antibodies are developed and approved for clinical use, the lessons learned with DARA will expand to deal with interference from future targeted therapies.

To The Editor: Many vascular access options, such as subcutaneous ports, are currently on the market for use in both medication infusion and for procedures, such as therapeutic plasma exchange (TPE), extracorporeal photopheresis (ECP), and red blood cell exchange (RBCx). Although most ports were not originally intended for such procedures, apheresis practitioners have used them for about 20 years. These devices yield flow rates of approximately 50 to 60 mL/min, which is enough for most apheresis applications. In general, subcutaneous ports are beneficial to patients requiring longterm repeated access for infusions or apheresis procedures. These ports minimize the psychosocial impact on patients by being less visible that central venous catheters (CVCs) or permcaths. CVCs also have a risk of being unintentionally pulled out by the patient during sleep or while exercising. The main downside to subcutaneous ports is the pain experienced during initial access of the port site (minimized with anesthetics or prophylactic injection of lidocaine). Like any other vascular access, ports may become clotted or infected, requiring removal and replacement. In April 2017, the FDA cleared the PowerFlow (Bard, Tempe, Arizona) for apheresis procedures and for other uses requiring repeat vascular access (eg, infusions, transfusions, and blood draws). This device has a unique design when compared to traditional ports. For example, the Vortex port (Angiodynamics, Latham, New York) sits parallel to the skin surface and requires perpendicular (90 ) access via a noncoring needle. In contrast, the PowerFlow is a cone-shaped titanium funnel that angles up from the subcutaneous tissue and is accessed much like an intravenous catheter at a 30 angle from the skin. This design reportedly allows for higher inlet flow rates (maximum 120-150 mL/min) and potentially less thrombus formation along the catheter surface. Figure 1B illustrates the access kit for the PowerFlow (left). Figure 1B demonstrates side-by-side placement of both ports in a patient undergoing TPE for Stiff Person Syndrome (Vortex left, PowerFlow right). Early reports on the usability of this port are encouraging. In February 2017 Transfusion Supplement, the Mayo Clinic (Scottsdale, Arizona) reported using the device to perform 70 ECP procedures, achieving flow rates of 30 to 50 mL/min for all patients with minimal pressure alarms. They also reported using the ports for plasma exchange at rates up to 100 mL/min. Our experience with the new ports is similar. We have 13 patients with PowerFlow ports. Three patients have only one PowerFlow, two patients have two PowerFlow ports, and eight patients have one PowerFlow and one Vortex. Seven patients have ports for ECP, three have ports for TPE, and three have ports for RBCx. A detailed analysis of our experience with two patients with at least 10 consecutive procedures with the Vortex port and 10 consecutive procedures with the PowerFlow port demonstrated statistically significant savings in terms of time to complete the procedures, as well as overall cost with the newer devices. Much of the cost savings came from the decreased need for thrombolytic agents prior to beginning a procedure and the time savings from faster inlet flow rates, fewer pressure alarms, and less time waiting for

Background: Deficiency of plasma ADAMTS13 activity resulting from acquired autoantibody against ADAMTS13 is the primary cause of immune thrombotic thrombocytopenic purpura (iTTP). Therapeutic plasma exchange plus corticosteroids and immunosuppression is the standard of care for patients with iTTP. However, mortality rate remains high and clinical factors or laboratory biomarkers that predict mortality are not fully established. Previous studies have demonstrated that plasma levels of histone-DNA complexes and cell-free DNA are dramatically elevated in patients with acute disease but reduced during remission. We hypothesize that elevated histone-DNA complexes or cell-free DNA may have a predictive role for mortality in patients with acute iTTP. Methods: 102 unique patients with a confirmed diagnosis of iTTP who underwent therapeutic plasma exchange (TPE) at UAB-Medical Center from April 2006 to December 2018 were enrolled into the study. Demographic information and laboratory parameters were collected on admission and during the follow-up. Plasma levels of histone-DNA complexes and cell-free DNA were determined by an enzyme-linked immunosorbent assay and PicoGreen dsDNA assay, respectively. Mann-Whitney, Fisher's exact, t test, log-rank test, and Cox proportional hazard regression analysis were performed to determine the significance of each marker in predicting death. Results: In this cohort, age was 44.7 ± 1.3 (mean ± SD) years old, 56.9% were female, 82.4% were African Americans, 61.8% had an initial episode, the median (IQR) body mass index (BMI) was 33.6 (29.3-41.5). 52.9% of patients had hypertension, 21.6% diabetes, 18.6% systemic lupus erythematous and 8.7% HIV. The overall mortality rate was 10.8% (11/102). Plasma levels, median (IQR), of histone-DNA complexes and cell-free DNA on admission were 56.3 (35.8-136.4) AU/mL and 952.2 (799.7-1431.4) ng/mL, respectively. Mann-Whitney test revealed that high plasma levels of histone-DNA complex (≥134.9 U/mL) (p=0.007) and cell-free DNA (≥952.2 ng/mL) (p=0.009) were associated with the increased risks of myocardial injury (e.g. elevated troponin). Cox proportional hazard regression analysis demonstrated that the increased levels of histone-DNA complexes and cell-free DNA were also predictive for the increased mortality rates in patients with iTTP with hazard ratios (HRs) of 4.1 (95% CI, 1.2-13.4) (p=0.02) and 8.5 (95% CI, 2.2-33.3 (p=0.002), respectively. Kaplan-Meier survival analysis revealed significant differences in the disease-free survival rates of patients with high levels (≥75 percentile) vs. low levels (<75 percentile) of plasma histone-DNA complexes and cell-free DNA, respectively (see Fig. 1). Conclusion: Our results demonstrate that the elevated plasma levels of histone-DNA complexes and cell-free DNA predict the worse outcome (e.g. the increased mortality rates) in patients with iTTP. *SD, standard deviation; IQR, interquartile range; 95% CI, 95% confidential interval. Disclosures Zheng: Ablynx/Sanofi: Consultancy, Speakers Bureau; Alexion: Speakers Bureau; Shire/Takeda: Research Funding; Clotsolution: Other: Co-Founder.

Heparin-induced thrombocytopenia (HIT) is a not-uncommon adverse effect of heparin exposure, with potentially serious and/or fatal thrombotic consequences. Recent studies looking at the off-label use of fondaparinux for HIT show similar efficacy and adverse-effect profiles, as well as improved costs, compared with some commonly used direct thrombin inhibitors. Although routine laboratory monitoring of fondaparinux-specific anti-Xa levels typically is not recommended, we present a case report that suggests fondaparinux monitoring may be needed in patients with hepatic impairment causing acquired antithrombin deficiency. We performed daily assessment of antithrombin- and fondaparinux-specific anti-Xa levels in a 50-year-old female of unknown ethnicity to ensure that fondaparinux dosing was maintained within an acceptable range. With this management strategy, the patient experienced no thrombotic or hemorrhagic complications during the hospital admission or the following 2 months in outpatient treatment.

Impaired response to P2Y12 receptor antagonists, such as clopidogrel and prasugrel, can have devastating consequences for patients that require prolonged or indefinite therapy with these agents, including those with a left ventricular assist device (LVAD). While loss-of-function (LOF) alleles in CYP2C19 have been elucidated as contributing to high on treatment platelet reactivity (HTPR) during clopidogrel therapy, genetic variations in the metabolic pathway of prasugrel have not been shown to elicit this same effect. Moreover, limited studies have assessed the effect of coexisting genetic variations in pharmacokinetic and pharmacodynamic pathways. Herein, we report a left ventricular assist device patient exhibiting high on treatment platelet reactivity during clopidogrel and prasugrel therapy. Genotyping revealed variants in pharmacokinetic (CYP2B6), and pharmacodynamic pathways, with multiple variants in P2Y12, the target receptor.

The AABB recently posted a bulletin (19-02) regarding their recommendations for the use of group O red blood cells (RBCs) during trauma. Though group O Rh(D)-negative RBC units are considered the 'safest', the demand of such units often exceeds the supply. Therefore, O Rh(D)-positive units are often used during the first parts of a massive transfusion protocol (MTP) or patients with particularly severe hemorrhage are switched over from O Rh(D)-negative to O Rh(D)-positive RBC units in order to preserve the O Rh(D)-negative supply. In light of these limitations, it is important to understand the risk of such policies to the patient. The reported risk of alloimmunization after exposure to Rh(D)-positive RBCs ranges widely from 3 to 70%. In response, we performed a retrospective review of 1,198 patients in our institution that had a MTP activation due to trauma. Of those patients, we focused on Rh(D)-negative patients that received at least 1 unit of Rh(D)-positive RBCs. Seventy-two patients met the criteria for inclusion, accounting for 6% of the total population. Of the 72 Rh(D)-negative patients, we identified 17% that formed new Rh group antibodies after exposure to Rh(D)-positive RBCS. All 10 of our alloimmunized patients (two of which were females of childbearing age) formed anti-D, while 3 patients also formed either anti-E or anti-C. Since this was a retrospective review, we did not perform repeated antibody screens for the entire study period, but did review all records for the entire period. We did note that we were more likely to detect an novel alloantibody if more antibody screens were performed during the patient's initial stay and during follow-up visits. We conclude that providing Rh(D) negative patients Rh(D) positive RBC units is not without risk and policies regarding such provisions should be carefully considered. As RBC shortages continue to be a part of daily practice, such issues may continue to be a challenge for the blood bank community.

OBJECTIVETo evaluate how clinical practice was affected by the change in direct antiglobulin testing (DAT) methodologies and subsequent stronger reported DAT results at our large academic medical center.METHODWe retrospectively reviewed DAT results of umbilical cord blood from infants with blood type A or B born to mothers with antibody-negative type O blood, based on records kept at the University of Alabama at Birmingham (UAB) Hospital, a 1400-bed academic medical center.RESULTSWe randomly chose 50 neonates with positive DAT results who had been tested using the tube method and 50 whose testing had used the gel method. Although 86% of results with the tube method were positive microscopically, 52% and 40% of the DAT results with the gel method were 1+ and 2+ positive, respectively. Further, we observed an increase in the number of neonates treated with phototherapy who had been tested using the gel method.CONCLUSIONWe report that DATs performed using the gel method had increased DAT strength compared with tube testing, which led to increased use of phototherapy by our clinical colleagues.

Background: Hypertriglyceridemia induced acute pancreatitis is associated with more severe clinical course than acute pancreatitis caused by other etiologies. Therapeutic plasma exchange (TPE) is a potential treatment for patients with severe hypertriglyceridemia induced acute pancreatitis due to its rapid effect in lowering triglycerides (TG) levels and reducing inflammatory cytokines. However, clinical data regarding the effectiveness and safety of TPE is limited. Methods: We retrospectively reviewed eight cases of hypertriglyceridemia induced acute pancreatitis and treated with TPE. Patients' demographic data, personal history, clinical course, laboratory results, apheresis data and clinical outcome were collected and analyzed. Results: At initial presentation, the average TG levels for the eight patients was 3381.6 mg/dl (SD: 1491.6 mg/ dl). Twelve procedures were performed on the eight patients in the study, and TG levels decreased by an average of 2673.2 mg/dl (SD: 2306.3 mg/dl) with a corresponding average reduction rate of 60.3 % (SD:21.1 %), ranging from 14.6%-84.9%. A 60 % or greater reduction was achieved in 66.7 % of all the procedures; however, the degree of reduction for each procedure was not predictable, even among repeat procedures on the same patient. Conclusions: Our study indicates that TPE is an effective and safe treatment option for patients with hypertriglyceridemia induced acute pancreatitis. However, due to the unpredictability of TG removal, repeat procedures may be necessary for some patients.

Introduction: Daratumumab is an IgG1k monoclonal antibody directed against CD38, a surface glycoprotein expressed on several cell types including erythrocytes and B lymphocytes at various stages in development, including bone marrow precursors and plasma cells. It was initially approved by the FDA in 2015 for the treatment of multiple myeloma and has since garnered additional approvals in other settings leading to a growing number of patients receiving daratumumab. Its anti-B lymphocyte properties are therapeutic in myeloma patients; however, it also binds CD38 on erythrocytes and circulates for up to six months after a dose. This creates a long-term problem when caring for these patients regarding transfusion needs and resources. In particular, daratumumab causes antibody screens to be panreactive, potentially masking the presence of clinically relevant antibodies. Mitigation of this effect requires specialized treatment with dithiothreitol (DTT)-treated reagent erythrocytes to release CD38 from the cell membrane. This step allows for more accurate detection of clinically relevant antibodies, with the noted exception of the Kell system as these antigens are also removed. Methods: When daratumumab was placed on formulary, we started weekly communication between the laboratory and clinical teams in order to establish best institutional practices. Additionally, a list of patients on daratumumab was created in order to track them across the institution and measure the impact of interventions on their care. These have prompted multiple interventions to improve the safety and efficiency of patients on daratumumab receiving transfusions. Results: As of January 2018, our laboratory began implementing in-house DTT testing and eliminated the need to send patient samples to a reference laboratory. Beginning in January 2019, DTT-antibody screens (ABSC) were captured in the electronic medical record (EMR). Over the next six months, 173 distinct DTT-ABSC were performed on 41 patients. Of these, 13 received at least one RBC transfusion for a total of 41 units, with 12 (29%) occurring as an outpatient and 29 (71%) as an inpatient. Importantly, all of these transfusions were on the same-day of the DTT-ABSC, reducing the burden of time and cost associated with travel, as well as the morbidities of delayed transfusion. This is a major step forward in patient care as there were previously no "same-day" transfusions when DTT-ABSC was sent to a reference laboratory. The previous reference laboratory turnaround time averaged 1165 minutes compared with 186 minutes for the in-house testing. These initiatives have also resulted in educational efforts, such as the creation of a daratumumab-specific transfusion consent form to be signed by the attending hematologist at the time of starting therapy, outlining the challenges associated with identifying blood for transfusion and documenting that the benefits of transfusion outweigh the potential risks. This form is valid indefinitely and has subverted previous clinical scenarios where inpatients on daratumumab required urgent/emergent transfusion without an in-house hematologist available to consent for the transfusion. Because DTT also eliminates Kell antigens, clinically relevant antibodies may go undetected in samples treated with DTT. Thus, it is our policy to use Kell-negative products for patients who are on daratumumab, unless the patient expresses the Kell antigen. Conclusions/Future Directions: Daratumumab therapy is becoming increasingly common in hematology practice. Awareness of the laboratory and clinical challenges that accompany its use and working to mitigate them will lead to safer and more timely patient care. In particular, in-house DTT-ABSC has led to same-day results and transfusion on the same outpatient visit. Next steps include additional educational efforts at an institutional level, establishing simple algorithms within the EMR linked with the order for daratumumab (e.g., automatic ABSC prior to administration), and refining our tracking system to better assess future interventions. Disclosures No relevant conflicts of interest to declare.