Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

The science or not behind deferrals of blood donors with a history of cancer.

BACKGROUND: In the United States (US), each blood center's medical director sets policy for donors with a cancer history. STUDY DESIGN AND METHODS: A subgroup of America's Blood Centers' (ABC) Scientific, Medical, and Technical Committee developed a survey to measure the determination of eligibility, policies for deferral and/or lookback when a donor reports a current diagnosis or history of cancer. A 31-question survey was sent to 47 ABC blood centers in North America via email. Survey results were compiled and literature evaluating the risk of cancer transmission by transfusion was reviewed. RESULTS: Responses were received from 37 centers (79%). Donors with a history of carcinoma or sarcoma who had completed treatment were accepted at 73% of centers with no further deferral. Donors with a history of leukemia or lymphoma were permanently deferred at 76% of centers. Donors with a myelodysplastic or myeloproliferative syndrome were deferred permanently at 86% of centers. Handling of donors with high white cell counts varied. Donors with cancer not in active treatment (i.e., prostate cancer) were subject to various deferrals. Center response to post-donation reports of cancer vary widely. Literature review yielded no evidence of transfusion-transmitted cancer. CONCLUSION: Cancer deferral policies vary widely among blood centers, and are not generally based on evidence, but on some aspect of the precautionary principle. As the donor population ages and so becomes more at risk of cancer, this approach may further reduce the available donor pool.

Patient blood management using dedicated personnel in the operating room-you get what you pay for.

A patient blood management (PBM) strategy can be applied to the process of intraoperative cell salvage for re-infusion during surgery. Stoneham et al. describe an effective PBM strategy applied to abdominal aortic aneurysm repair and emphasise the importance of a qualified and experienced intraoperative cell salvage practitioner to improve the safety and effectiveness of the approach. Commentary on: Stoneham et al. Intraoperative cell salvage using swab wash and serial thromboelastography in elective abdominal aortic aneurysm surgery involving massive blood loss. Br J Haematol 2023;200:652-659.

CMV screening of group-specific orders-good stewardship of the blood supply.

BACKGROUND: In addition to antigen-negative red blood cells (RBC), Immunohematology Reference Laboratories (IRL) must provide RBCs that are cytomegalovirus (CMV) seronegative. Due to high percentage of CMV seropositive individuals, it is challenging to find CMV and antigen-negative RBC. The IRL selects predominantly group O donors tested for CMV, and these RBC are sometimes needed to fill orders for nongroup O patients. This study evaluated units sent that were out of group to fulfill CMV-seronegative requests. STUDY DESIGN AND METHODS: Requests for CMV-seronegative and antigen-negative RBCs were divided into Period 1 (January 1, 2019-February 29, 2020) before intervention and Period 2 (March 1, 2020-May 31, 2020) post intervention. ABO Rh units requested were compared to ABO Rh units provided. RESULTS: Period 1: 537 CMV-seronegative RBC units were provided. 99/188(52.66%) B-positive requests were fulfilled using O RBCs. 58/504 (11.51%) of D-negative units were sent to D-positive patients. Period 2: 119 CMV-seronegative RBC units were provided. 18/51 (35.29%) B positive requests were fulfilled using O RBCs. Only 7/113 (6.19%) D-negative units were sent to D-positive patients. DISCUSSION: For 239/656 (36.43%) CMV-seronegative antigen orders requested for B-positive patients, more than half of these orders were filled with O RBCs. To decrease group O usage for nongroup O patients, the IRL practice has changed to increase CMV testing for group B donors. Since the change in algorithm, there was a 17.37% decrease group O usage for group B patients.

Maintaining adequate donations and a sustainable blood supply: Lessons learned.

BACKGROUND: The availability of a safe blood supply is a key component of transfusion medicine. A decade of decreased blood use, decreased payment for products, and a dwindling donor base have placed the sustainability of the US blood supply at risk. STUDY DESIGN AND METHODS: A literature review was performed for blood center (BC) and hospital disaster management, chronically transfusion-dependent diseases, and appropriate use of group O-negative red blood cells (RBCs), and the Choosing Wisely campaign. The aim was to identify current practice and to make recommendations for BC and hospital actions. RESULTS: While BCs are better prepared to handle disasters than after the 9/11 attacks, messaging to the public remains difficult, as donors often do not realize that blood transfused during a disaster was likely collected before the event. BCs and transfusion services should participate in drafting disaster response plans. Hospitals should maintain inventories adequate for patients in the event supply is disrupted. Providing specialty products for transfusion-dependent patients can strain collections, lead to increased use of group O RBCs, and create logistical inventory challenges for hospitals. The AABB Choosing Wisely initiative addresses overuse of blood components to optimally use this precious resource. Group O-negative RBCs should be transfused only to patients who truly need them. CONCLUSIONS: Collecting and maintaining a blood supply robust enough to handle disasters and transfusion-dependent patients in need of specialty products is challenging. Collaboration of all parties should help to optimize resources, ensure appropriate collections, improve patient care, and ultimately result in a robust, sustainable blood supply.

An international effort and use of social media to save a young girl.

BACKGROUND AND OBJECTIVES: A 2-year-old female with neuroblastoma needed In(b-), E- red blood cells (RBCs). No units were available at the blood centre (BC) nor in the rare donor programme member's inventories. BC's Immunohematology Reference Laboratory (IRL) and its marketing department concentrated on recruiting and testing those donors more likely to be antigen negative based on ethnicity. MATERIALS AND METHODS: The BC's communication plan utilized social and traditional media to assist in the search for In(b-) blood. Media strategies directed donors in the United States (US) and Canada to go to their nearest BC for collection, tagging and testing of units. Two segments from each donation were shipped overnight to the BC's IRL (associated with the patient) for testing. Diluted anti-Inb sera was tested by microtechniques to conserve resources. Additionally, the American Rare Donor Program (ARDP) facilitated the international searches and acted as a liaison to the Food and Drug Administration (FDA). RESULTS: More than 25 000 people responded to the appeal. Seventy-seven BCs submitted segments from 4197 units. Two donors were In(b-) but E+ and thus not compatible with the patient but were submitted to ARDP for future needs. The prevalence of In(b-) units identified in the search was 0·048%. In total, five known In(b-) donors, two from the US and three from international sources, provided units for this patient. CONCLUSION: Social media sparked a viral response to the rare blood need. While a match was not found among the units tested, domestic and international searches were able to meet the patient's blood needs.

Evaluation of Iron Stores by Zinc Protoporphyrin Analysis in Blood Donors.

BACKGROUND: Zinc protoporphyrin (ZPP) testing has been studied previously as a substitute for ferritin (fer) testing of blood donors in determining iron stores. OBJECTIVE: To determine whether ZPP testing could be performed using specimens collected via the capillary (cap) finger-stick (FS) method, similar to predonation hemoglobin (HB) testing. Also, we evaluated the correlation among FS HB, venous (ven) ZZP, FS ZPP, and ven fer levels as predictors of iron depletion. METHODS: Blood donations from 328 study participants were evaluated using FS HB assay; we also performed ven ZPP, cap ZPP, and ven fer testing. We assessed the donors for subclinical iron deficiency (fer levels <26 ng/mL and ZPP levels >100 µmol/mol heme). RESULTS: Subclinical iron deficiency was present among first-time and repeat blood donors at all HB levels. Variation among test results (FS HB, ven fer, ven ZPP, and FS ZPP) was statistically significant (P <.001). CONCLUSION: Insufficient correlation existed regarding FS HB and ven fer test results to support use of ZPP to determine iron stores in blood donors.

Correlation between the papanicolaou stain and the Wright-Giemsa stain in body fluids: a quality assurance study.

OBJECTIVE: To compare the use of Papanicolaou and Wright-Giemsa stains for the evaluation of body fluids in cytology and hematology laboratories and determine whether other factors account for discrepancies in diagnosis. STUDY DESIGN: We retrospectively reviewed cytopathology reports of peritoneal, pleural, and cerebrospinal fluids received by hematology and cytology laboratories for 1 year. Cases were divided into 3 categories-benign, atypical, and malignant--and slides of discrepant diagnoses were reviewed. RESULTS: During this period, 198 of 3212 (0.61%) cases received by the hematology laboratory and 252 of 4402 (0.57%) cases received by the cytology laboratory were diagnosed as malignant or atypical. Of 3212 cases simultaneously received by the cytology and hematology laboratories, 17 diagnosed as malignant by hematology were diagnosed benign by cytology (sensitivity 96%). Sixteen cases diagnosed as malignant by cytology were diagnosed as benign by hematology (sensitivity 97%). No benign cases were diagnosed as malignant (specificity 100%). Review of the glass slides of the discrepant cases revealed 8 cases undercalled by hematology and 7 cases undercalled by cytology. CONCLUSION: Papanicolaou stain is superior for carcinoma and Wright-Giemsa stain for hematopoietic disorders, but used together they may reduce false negative results. Delays in processing, staining technique, and interobserver variability contribute to discrepancy.