Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice
Background: Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted vari...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-09-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416303553 |
| _version_ | 1818313908660731904 |
|---|---|
| author | David O. Osei-Hwedieh, PhD Tamir Kanias, PhD Claudette St. Croix, PhD Morgan Jessup, BS Zeyu Xiong, MD Derek Sinchar, BS Jonathan Franks, MS Qinzi Xu, MD Enrico M. Novelli, MD Jonas T. Sertorio, PhD Karin Potoka, MD Robert J. Binder, PhD Swati Basu, PhD Andrea M. Belanger, PhD Daniel B. Kim-Shapiro, PhD Darrell Triulzi, MD Janet S. Lee, MD Mark T. Gladwin, MD |
| author_facet | David O. Osei-Hwedieh, PhD Tamir Kanias, PhD Claudette St. Croix, PhD Morgan Jessup, BS Zeyu Xiong, MD Derek Sinchar, BS Jonathan Franks, MS Qinzi Xu, MD Enrico M. Novelli, MD Jonas T. Sertorio, PhD Karin Potoka, MD Robert J. Binder, PhD Swati Basu, PhD Andrea M. Belanger, PhD Daniel B. Kim-Shapiro, PhD Darrell Triulzi, MD Janet S. Lee, MD Mark T. Gladwin, MD |
| author_sort | David O. Osei-Hwedieh, PhD |
| collection | DOAJ |
| description | Background: Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear.
Methods: We explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hbatm1PazHbbtm1TowTg(HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS).
Findings: Human and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intravascular hemolysis, but by enhanced sequestration in the spleen, kidney and liver. HbAS RBCs are intrinsically different from HbAA RBCs, with reduced membrane deformability as cells age in cold storage, leading to accelerated clearance of transfused HbAS RBCs by entrapment in organ microcirculation.
Interpretation: The common genetic variant HbAS enhances RBC storage dysfunction and raises provocative questions about the use of HbAS RBCs at the limits of approved storage. |
| first_indexed | 2024-12-13T08:41:13Z |
| format | Article |
| id | doaj.art-c730e68de83e4423ba5cde82a1893e15 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T08:41:13Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-c730e68de83e4423ba5cde82a1893e152022-12-21T23:53:32ZengElsevierEBioMedicine2352-39642016-09-0111C23924810.1016/j.ebiom.2016.08.006Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in MiceDavid O. Osei-Hwedieh, PhD0Tamir Kanias, PhD1Claudette St. Croix, PhD2Morgan Jessup, BS3Zeyu Xiong, MD4Derek Sinchar, BS5Jonathan Franks, MS6Qinzi Xu, MD7Enrico M. Novelli, MD8Jonas T. Sertorio, PhD9Karin Potoka, MD10Robert J. Binder, PhD11Swati Basu, PhD12Andrea M. Belanger, PhD13Daniel B. Kim-Shapiro, PhD14Darrell Triulzi, MD15Janet S. Lee, MD16Mark T. Gladwin, MD17Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, United StatesDivision of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesCenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Physics, Wake Forest University, Winston-Salem, NC, United StatesDepartment of Physics, Wake Forest University, Winston-Salem, NC, United StatesDepartment of Physics, Wake Forest University, Winston-Salem, NC, United StatesInstitute for Transfusion Medicine, ITxM, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesPittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United StatesBackground: Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear. Methods: We explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hbatm1PazHbbtm1TowTg(HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS). Findings: Human and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intravascular hemolysis, but by enhanced sequestration in the spleen, kidney and liver. HbAS RBCs are intrinsically different from HbAA RBCs, with reduced membrane deformability as cells age in cold storage, leading to accelerated clearance of transfused HbAS RBCs by entrapment in organ microcirculation. Interpretation: The common genetic variant HbAS enhances RBC storage dysfunction and raises provocative questions about the use of HbAS RBCs at the limits of approved storage.http://www.sciencedirect.com/science/article/pii/S2352396416303553Sickle cell traitRed cell storageBloodPost-transfusion survivalTransfusion practiceRBC hemolysis |
| spellingShingle | David O. Osei-Hwedieh, PhD Tamir Kanias, PhD Claudette St. Croix, PhD Morgan Jessup, BS Zeyu Xiong, MD Derek Sinchar, BS Jonathan Franks, MS Qinzi Xu, MD Enrico M. Novelli, MD Jonas T. Sertorio, PhD Karin Potoka, MD Robert J. Binder, PhD Swati Basu, PhD Andrea M. Belanger, PhD Daniel B. Kim-Shapiro, PhD Darrell Triulzi, MD Janet S. Lee, MD Mark T. Gladwin, MD Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice EBioMedicine Sickle cell trait Red cell storage Blood Post-transfusion survival Transfusion practice RBC hemolysis |
| title | Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice |
| title_full | Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice |
| title_fullStr | Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice |
| title_full_unstemmed | Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice |
| title_short | Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice |
| title_sort | sickle cell trait increases red blood cell storage hemolysis and post transfusion clearance in mice |
| topic | Sickle cell trait Red cell storage Blood Post-transfusion survival Transfusion practice RBC hemolysis |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416303553 |
| work_keys_str_mv | AT davidooseihwediehphd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT tamirkaniasphd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT claudettestcroixphd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT morganjessupbs sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT zeyuxiongmd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT dereksincharbs sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT jonathanfranksms sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT qinzixumd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT enricomnovellimd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT jonastsertoriophd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT karinpotokamd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT robertjbinderphd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT swatibasuphd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT andreambelangerphd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT danielbkimshapirophd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT darrelltriulzimd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT janetsleemd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice AT marktgladwinmd sicklecelltraitincreasesredbloodcellstoragehemolysisandposttransfusionclearanceinmice |