Pub Date : 2024-04-02eCollection Date: 2024-12-01DOI: 10.1159/000536322
Sven Arends, Michael Thomas, Michael Nosch, Thomas Droll, Denise Zwanziger, Thorsten Brenner, Ali Haddad
Background: The use of cell salvage and autologous blood transfusion is an important and widespread method of blood conservation during surgeries with expected high blood loss. The continuous autotransfusion device CATSmart® (Fresenius Kabi, Germany) contains two new washing programs on the device called Flex wash 3 and Flex wash 5. To the best of our knowledge, there are no published clinical data regarding the performance of the two new washing programs.
Methods: In total, 69 patients undergoing cardiac or orthopedic surgery were included in this randomized, controlled, bicentric trial to validate the red cell separation process and washout quality of Flex wash 3 compared to Flex wash 5. After washing, the primary quality target was to determine hematocrit value, recovery rate, albumin, and total protein elimination rate in the packed red cells (PRCs). The secondary objective was to assess the elimination of heparin by measuring the factor anti-Xa activity by a 1- and 2-stage assay in PRC after washing.
Results: In the whole cohort of patients, hematocrit was 16.00% [9.15%; 21.30%] (median [Q1; Q3]) in the wound blood and 69.90% [51.10%; 80.90%] in the PRC resulting in a recovery rate of 63.92% [47.06%; 88.13%]. The albumin elimination rate was 98.77% [97.94%; 99.27%], and the total protein elimination rate was 98.85% [97.76%; 99.42%]. The heparin elimination rate was 99.95% [99.90%; 99.97%] in the 1-stage assay and 99.70% [99.41%; 99.87%] in the 2-stage assay. There was no difference between Flex wash 3 and Flex wash 5 washing procedure regarding the recovery rate 63.75% [46.64%; 78.65%] versus 67.89% [47.20%; 92.69%] (p = 0.85), albumin elimination rate 98.74% [97.67%; 99.27%] versus 98.78% [98.10%; 99.28%] (p = 0.97), protein elimination rate 98.79% [97.94%; 99.47%] versus 98.92% [97.58%; 99.42%] (p = 0.88), and anti-Xa elimination rate in the 1-stage assay 99.94% [99.79%; 99.97%] versus 99.95% [99.92%; 99.97%] (p = 0.24) and in 2-stage assay 99.66% [99.20%; 99.86%] versus 99.77% [99.47%; 99.90%] (p = 0.23).
Conclusions: The two new washing procedures, Flex wash 3 and Flex wash 5, enable sufficient and comparable red cell separation and washout quality of albumin, total protein, as well as heparin.
{"title":"Cell Salvage Using the Autotransfusion Device CATSmart<sup>®</sup>: A Randomized Controlled Bicentric Trial Evaluating the Quality of Two New Flex Wash Programs.","authors":"Sven Arends, Michael Thomas, Michael Nosch, Thomas Droll, Denise Zwanziger, Thorsten Brenner, Ali Haddad","doi":"10.1159/000536322","DOIUrl":"10.1159/000536322","url":null,"abstract":"<p><strong>Background: </strong>The use of cell salvage and autologous blood transfusion is an important and widespread method of blood conservation during surgeries with expected high blood loss. The continuous autotransfusion device CATSmart<sup>®</sup> (Fresenius Kabi, Germany) contains two new washing programs on the device called Flex wash 3 and Flex wash 5. To the best of our knowledge, there are no published clinical data regarding the performance of the two new washing programs.</p><p><strong>Methods: </strong>In total, 69 patients undergoing cardiac or orthopedic surgery were included in this randomized, controlled, bicentric trial to validate the red cell separation process and washout quality of Flex wash 3 compared to Flex wash 5. After washing, the primary quality target was to determine hematocrit value, recovery rate, albumin, and total protein elimination rate in the packed red cells (PRCs). The secondary objective was to assess the elimination of heparin by measuring the factor anti-Xa activity by a 1- and 2-stage assay in PRC after washing.</p><p><strong>Results: </strong>In the whole cohort of patients, hematocrit was 16.00% [9.15%; 21.30%] (median [Q1; Q3]) in the wound blood and 69.90% [51.10%; 80.90%] in the PRC resulting in a recovery rate of 63.92% [47.06%; 88.13%]. The albumin elimination rate was 98.77% [97.94%; 99.27%], and the total protein elimination rate was 98.85% [97.76%; 99.42%]. The heparin elimination rate was 99.95% [99.90%; 99.97%] in the 1-stage assay and 99.70% [99.41%; 99.87%] in the 2-stage assay. There was no difference between Flex wash 3 and Flex wash 5 washing procedure regarding the recovery rate 63.75% [46.64%; 78.65%] versus 67.89% [47.20%; 92.69%] (<i>p</i> = 0.85), albumin elimination rate 98.74% [97.67%; 99.27%] versus 98.78% [98.10%; 99.28%] (<i>p</i> = 0.97), protein elimination rate 98.79% [97.94%; 99.47%] versus 98.92% [97.58%; 99.42%] (<i>p</i> = 0.88), and anti-Xa elimination rate in the 1-stage assay 99.94% [99.79%; 99.97%] versus 99.95% [99.92%; 99.97%] (<i>p</i> = 0.24) and in 2-stage assay 99.66% [99.20%; 99.86%] versus 99.77% [99.47%; 99.90%] (<i>p</i> = 0.23).</p><p><strong>Conclusions: </strong>The two new washing procedures, Flex wash 3 and Flex wash 5, enable sufficient and comparable red cell separation and washout quality of albumin, total protein, as well as heparin.</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 6","pages":"367-372"},"PeriodicalIF":1.9,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-22eCollection Date: 2024-06-01DOI: 10.1159/000534302
[This corrects the article DOI: 10.1159/000533624.].
[此处更正了文章 DOI：10.1159/000533624]。
{"title":"Erratum.","authors":"","doi":"10.1159/000534302","DOIUrl":"https://doi.org/10.1159/000534302","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1159/000533624.].</p>","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"51 3","pages":"198"},"PeriodicalIF":1.9,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lina S. Silva-Bermúdez, D. Heidenreich, Stefan A. Klein, Patrick Wuchter, Harald Klüter, Sabine Kayser
Introduction: Major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common practice and represents a challenging transfusion scenario. Prolonged thrombocytopenia with increased platelet transfusion needs is one of its reported adverse effects, and this has been linked to the persistence of recipient anti-donor isoagglutinins. Case Presentation: A 55-year-old male patient, O Rh(D)-positive, with chronic myelomonocytic leukemia underwent major incompatible allo-HCT from a A Rh(D)-negative donor. He presented with prolonged thrombocytopenia and multiple transfusion reactions after A Rh(D)-negative platelet transfusions. Considering the outcomes of numerous examinations, we tested the anti-A1 titers, finding a significant persistence of anti-donor isoagglutinins. We limited platelet transfusions to blood group O Rh(D)-negative donors, which significantly decreased the requirement for platelet transfusions. In addition, the transfusion reactions ceased. Conclusion: In case of transfusion reactions against platelet products in major ABO-incompatible allo-HCT patients, isoagglutinin monitoring should be considered and a change in the platelet transfusion protocol may be beneficial in patients presenting high isotiters against recipient’s blood type.
导言：ABO不相容异基因造血干细胞移植（allo-HCT）是一种常见的治疗方法，也是一种具有挑战性的输血方案。据报道，血小板减少时间延长、血小板输注需求增加是其不良反应之一，这与受体抗供体异凝集素的持续存在有关。病例介绍：一名 55 岁的男性患者，O 型 Rh（D）阳性，患有慢性粒单核细胞白血病，接受了来自 A 型 Rh（D）阴性供体的主要不相容异体造血干细胞移植。在输注 A 型 Rh(D) 阴性血小板后，他出现了长时间血小板减少和多次输血反应。考虑到多次检查的结果，我们检测了抗 A1 滴度，发现抗供体异凝集素显著持续存在。我们将血小板输注限制在血型为 O 型 Rh（D）阴性的献血者身上，这大大降低了血小板输注的需求量。此外，输血反应也停止了。结论如果主要 ABO 血型不相容的异体肝移植患者出现血小板产品输血反应，应考虑进行等凝集素监测，改变血小板输注方案可能对出现受体血型高等凝集素的患者有益。
{"title":"Prolonged Thrombocytopenia and Severe Transfusion Reaction after ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Chronic Myelomonocytic Leukemia","authors":"Lina S. Silva-Bermúdez, D. Heidenreich, Stefan A. Klein, Patrick Wuchter, Harald Klüter, Sabine Kayser","doi":"10.1159/000534272","DOIUrl":"https://doi.org/10.1159/000534272","url":null,"abstract":"Introduction: Major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common practice and represents a challenging transfusion scenario. Prolonged thrombocytopenia with increased platelet transfusion needs is one of its reported adverse effects, and this has been linked to the persistence of recipient anti-donor isoagglutinins. Case Presentation: A 55-year-old male patient, O Rh(D)-positive, with chronic myelomonocytic leukemia underwent major incompatible allo-HCT from a A Rh(D)-negative donor. He presented with prolonged thrombocytopenia and multiple transfusion reactions after A Rh(D)-negative platelet transfusions. Considering the outcomes of numerous examinations, we tested the anti-A1 titers, finding a significant persistence of anti-donor isoagglutinins. We limited platelet transfusions to blood group O Rh(D)-negative donors, which significantly decreased the requirement for platelet transfusions. In addition, the transfusion reactions ceased. Conclusion: In case of transfusion reactions against platelet products in major ABO-incompatible allo-HCT patients, isoagglutinin monitoring should be considered and a change in the platelet transfusion protocol may be beneficial in patients presenting high isotiters against recipient’s blood type.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"35 33","pages":""},"PeriodicalIF":2.2,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139442847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD – Peter Schlenke, PhD – Peter Bugert, MD Beate Mayer, MD Axel Pruß, MD Franz F. Wagner, MD Patrick Wuchter, PhD – Jason Acker, MD Gregor Bein, MD – Reinhard Burger, Robert Koch, PhD Toni Cathomen, PhD Jens Dreier, MD Hermann Eichler, MD – Andreas Humpe, MD Harald Klüter, MD – Jens Meier, MD – Rainer Moog, German Red, PhD – Bristol Andrew D. Mumford, CardioVascular, PhD – Thierry Peyrard, MD – Erwin Strasser, PhD – Pieter F. van der Meer, MD – Mark H. Yazer, E. Strasser, J. Piñeyroa, J. Cid, M. Lozano, P. Schlenke, von Heymann, Berlin Lier, H. Cologne, C. Rosenthal, L. Kaufner, Berlin, P.F.W. Strengers, Amsterdam, J. Cottrell, A. Al Sanani, I. Ogu, D. Chaffin, WV Huntington, D’Alessandro, P. A. Bugert, Research Articles, Meta-Analysis Qin, X. G. Han
{"title":"Contents Vol. 50, 2023","authors":"MD – Peter Schlenke, PhD – Peter Bugert, MD Beate Mayer, MD Axel Pruß, MD Franz F. Wagner, MD Patrick Wuchter, PhD – Jason Acker, MD Gregor Bein, MD – Reinhard Burger, Robert Koch, PhD Toni Cathomen, PhD Jens Dreier, MD Hermann Eichler, MD – Andreas Humpe, MD Harald Klüter, MD – Jens Meier, MD – Rainer Moog, German Red, PhD – Bristol Andrew D. Mumford, CardioVascular, PhD – Thierry Peyrard, MD – Erwin Strasser, PhD – Pieter F. van der Meer, MD – Mark H. Yazer, E. Strasser, J. Piñeyroa, J. Cid, M. Lozano, P. Schlenke, von Heymann, Berlin Lier, H. Cologne, C. Rosenthal, L. Kaufner, Berlin, P.F.W. Strengers, Amsterdam, J. Cottrell, A. Al Sanani, I. Ogu, D. Chaffin, WV Huntington, D’Alessandro, P. A. Bugert, Research Articles, Meta-Analysis Qin, X. G. Han","doi":"10.1159/000535411","DOIUrl":"https://doi.org/10.1159/000535411","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"145 3","pages":"568 - 575"},"PeriodicalIF":2.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139012756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Frietsch, Maria B. Rondinelli, Jerrold H. Levy
{"title":"Congratulation, Appraisal, and Comment on the 25 Years Anniversary of Serious Hazards of Blood Transfusion","authors":"Thomas Frietsch, Maria B. Rondinelli, Jerrold H. Levy","doi":"10.1159/000532049","DOIUrl":"https://doi.org/10.1159/000532049","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"1 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139233540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Transfusion of platelets is a life-saving medical strategy used worldwide to treat patients with thrombocytopenia as well as platelet function disorders. Summary: Until the end of 1960s, platelets were stored in the cold because of their superior hemostatic functionality. Cold storage of platelets was then abandoned due to better posttransfusion recovery and survival of room temperature (RT)-stored platelets, demonstrated by radioactive labeling studies. Based on these findings, RT became the standard condition to store platelets for clinical applications. Evidence shows that RT storage increases the risk of septic transfusion reactions associated with bacterial contamination. Therefore, the storage time is currently limited to 4–7 days, according to the national guidelines, causing a constant challenge to cover the clinical request. Despite the enormous efforts made to optimize storage conditions of platelets, the quality and efficacy of platelets still decrease during the short storage time at RT. In this context, during the last years, cold storage has seen a renaissance due to the better hemostatic functionality, reduced risk of bacterial contamination, and potentially longer storage time. Key Messages: In this review, we will focus on the impact of cold storage on the in vitro platelet functions as promising alternative storage temperature for future medical applications.
{"title":"In vitro Hemostatic Functions of Cold-Stored Platelets","authors":"J. Kirschall, G. Uzun, T. Bakchoul, I. Marini","doi":"10.1159/000533735","DOIUrl":"https://doi.org/10.1159/000533735","url":null,"abstract":"Background: Transfusion of platelets is a life-saving medical strategy used worldwide to treat patients with thrombocytopenia as well as platelet function disorders. Summary: Until the end of 1960s, platelets were stored in the cold because of their superior hemostatic functionality. Cold storage of platelets was then abandoned due to better posttransfusion recovery and survival of room temperature (RT)-stored platelets, demonstrated by radioactive labeling studies. Based on these findings, RT became the standard condition to store platelets for clinical applications. Evidence shows that RT storage increases the risk of septic transfusion reactions associated with bacterial contamination. Therefore, the storage time is currently limited to 4–7 days, according to the national guidelines, causing a constant challenge to cover the clinical request. Despite the enormous efforts made to optimize storage conditions of platelets, the quality and efficacy of platelets still decrease during the short storage time at RT. In this context, during the last years, cold storage has seen a renaissance due to the better hemostatic functionality, reduced risk of bacterial contamination, and potentially longer storage time. Key Messages: In this review, we will focus on the impact of cold storage on the in vitro platelet functions as promising alternative storage temperature for future medical applications.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"131 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139267885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaxuan Yang, Aijing Li, Minghao Li, Shulin Ruan, Luyi Ye
Introduction: The Vel– phenotype is a rare blood group, and it is challenging for identifying this phenotype due to limited available reagents. Moreover, there are relatively few studies on genomic editing of erythroid antigens and generation of knockout (KO) cell lines at present. Methods: To identify the high-efficiency small-guiding RNA (sgRNA) sequence, candidate sgRNAs were transfected into HEK 293T cells and analyzed using Sanger sequencing. Following this, the high-efficiency sgRNA was transfected into K562 cells using lentivirus transduction to generate KO Vel blood group gene cells. The expression of the Vel protein was detected using Western blot on single-cell clones. Additionally, flow cytometry was used to detect the erythroid markers CD235a and CD71. Hemoglobin quantification and Giemsa staining were also performed to evaluate the erythroid differentiation of KO clones induced by hemin. Results: The high-efficiency sgRNA was successfully obtained and used for CRISPR-Cas9 editing in K562 cells. After limiting dilution and screening, two KO clones had either deleted 2 or 4 bases and showed no expression of the Vel protein. In the hemin-induced KO clone, there was a significant difference in erythroid marker and hemoglobin quantification compared to untreated cells. The morphological changes were also observed for the hemin-induced KO clone. Conclusion: In this study, a highly efficient sgRNA was screened out and used to generate Vel erythroid antigen KO single-cell clones in K562 cells. The edited cells could then be induced to undergo erythroid differentiation with the use of hemin.
{"title":"CRISPR/Cas9-Editing K562 Cell Line as a Potential Tool in Transfusion Applications: Knockout of Vel Antigen Gene","authors":"Jiaxuan Yang, Aijing Li, Minghao Li, Shulin Ruan, Luyi Ye","doi":"10.1159/000534012","DOIUrl":"https://doi.org/10.1159/000534012","url":null,"abstract":"<b><i>Introduction:</i></b> The Vel– phenotype is a rare blood group, and it is challenging for identifying this phenotype due to limited available reagents. Moreover, there are relatively few studies on genomic editing of erythroid antigens and generation of knockout (KO) cell lines at present. <b><i>Methods:</i></b> To identify the high-efficiency small-guiding RNA (sgRNA) sequence, candidate sgRNAs were transfected into HEK 293T cells and analyzed using Sanger sequencing. Following this, the high-efficiency sgRNA was transfected into K562 cells using lentivirus transduction to generate KO Vel blood group gene cells. The expression of the Vel protein was detected using Western blot on single-cell clones. Additionally, flow cytometry was used to detect the erythroid markers CD235a and CD71. Hemoglobin quantification and Giemsa staining were also performed to evaluate the erythroid differentiation of KO clones induced by hemin. <b><i>Results:</i></b> The high-efficiency sgRNA was successfully obtained and used for CRISPR-Cas9 editing in K562 cells. After limiting dilution and screening, two KO clones had either deleted 2 or 4 bases and showed no expression of the Vel protein. In the hemin-induced KO clone, there was a significant difference in erythroid marker and hemoglobin quantification compared to untreated cells. The morphological changes were also observed for the hemin-induced KO clone. <b><i>Conclusion:</i></b> In this study, a highly efficient sgRNA was screened out and used to generate Vel erythroid antigen KO single-cell clones in K562 cells. The edited cells could then be induced to undergo erythroid differentiation with the use of hemin.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"230 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135876462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick Meybohm, Lotta Hof, Suma Choorapoikayil, Kai Zacharowski
{"title":"Patient Blood Management: We Still Have Work to Do","authors":"Patrick Meybohm, Lotta Hof, Suma Choorapoikayil, Kai Zacharowski","doi":"10.1159/000534087","DOIUrl":"https://doi.org/10.1159/000534087","url":null,"abstract":"","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"35 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134973216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eungjun Yoon, Tae Yeul Kim, Hyungsuk Kim, Duck Cho
Introduction: Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. Methods: Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jka) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fyb and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. Results: Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. Discussion: Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment.
{"title":"Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing","authors":"Eungjun Yoon, Tae Yeul Kim, Hyungsuk Kim, Duck Cho","doi":"10.1159/000534273","DOIUrl":"https://doi.org/10.1159/000534273","url":null,"abstract":"<b><i>Introduction:</i></b> Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. <b><i>Methods:</i></b> Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jk<sup>a</sup>) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fy<sup>b</sup> and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. <b><i>Results:</i></b> Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. <b><i>Discussion:</i></b> Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment.","PeriodicalId":23252,"journal":{"name":"Transfusion Medicine and Hemotherapy","volume":"35 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135219224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johannes-Moritz von Behren, Jan Wesche, Andreas Greinacher, Konstanze Aurich
Introduction: Before being implemented in daily clinical routine, new production strategies for platelet concentrates (PCs) must be validated for their efficacy. Besides in vitro testing, the establishment of new methods requires the labeling of platelets for in vivo studies of platelets’ survival and recovery. Indocyanine green (ICG) is a Food and Drug Administration-approved near-infrared (NIR) fluorescent dye for diagnostic use in vivo, suitable for non-radioactive direct cell labeling of platelets. Methods: Platelets from PCs in storage solutions with different plasma concentrations were labeled with ICG up to concentrations of 200 μm. Whole blood (WB) was used as an ex vivo matrix to monitor the labeling stability of ICG-labeled platelets. The impact of labeling processes was assessed by the quantification of CD62P expression and PAC-1 binding as platelet function markers. Platelet aggregation was analyzed by light transmission aggregometry. ICG-labeling efficiency and stability of platelets were determined by flow cytometry. Results: Platelets from PCs could be successfully labeled with 10 μm ICG after 1 and 4 days of storage. The best labeling efficiency of 99.8% ± 0.1% (immediately after labeling) and 81% ± 6.2% (after 24 h incubation with WB) was achieved by plasma replacement by 100% platelet additive solution for the labeling process. Since the washing process slightly impaired platelet function, ICG labeling itself did not affect platelets. Immediately after the ICG-labeling process, plasma was re-added, resulting in a recovered platelet function. Conclusion: We developed a Good Manufacturing Practice compatible protocol for ICG fluorescent platelet labeling suitable for survival and recovery studies in vivo as a non-radioactive labeling alternative.
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