{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T09:01:07Z","timestamp":1792918867101,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,6,7]]},"abstract":"<jats:p>Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in \u22481:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin \u03b1IIb\u03b23. Transfusion therapy is frequently inadequate because patients often generate antibodies to \u03b1IIb\u03b23, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 \u03b1IIb\u03b23 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to \u03b1IIb\u03b23\u2019s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with \u2264135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to \u03b1IIb\u03b23 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.<\/jats:p>","DOI":"10.1073\/pnas.1016394108","type":"journal-article","created":{"date-parts":[[2011,5,24]],"date-time":"2011-05-24T00:31:06Z","timestamp":1306197066000},"page":"9583-9588","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Platelet gene therapy improves hemostatic function for integrin \u03b1IIb\u03b23-deficient dogs"],"prefix":"10.1073","volume":"108","author":[{"given":"Juan","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226;"},{"name":"Midwest Athletes Against Childhood Cancer Fund Research Center, Milwaukee, WI 53226;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Biomedical Resource Center, Medical College of Wisconsin, Milwaukee, WI 53226;"},{"name":"Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Boudreaux","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily M.","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226;"},{"name":"Midwest Athletes Against Childhood Cancer Fund Research Center, Milwaukee, WI 53226;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy B.","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevasti B.","family":"Koukouritaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226;"},{"name":"Midwest Athletes Against Childhood Cancer Fund Research Center, Milwaukee, WI 53226;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Cornetta","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226;"},{"name":"Midwest Athletes Against Childhood Cancer Fund Research Center, Milwaukee, WI 53226;"},{"name":"Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,5,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-09-0568"},{"key":"e_1_3_3_2_2","first-page":"113","article-title":"Hereditare hamorrhagische thrombasthenie: Ein beitrag zur pathologie dr blut plattchen","volume":"88","author":"Glanzmann E","year":"1918","unstructured":"E Glanzmann, Hereditare hamorrhagische thrombasthenie: Ein beitrag zur pathologie dr blut plattchen. 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